{"@context":"https://w3id.org/ro/crate/1.1/context","@type":"Dataset","id":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","name":"Research Synthesis: Oral Microbiome Periodontal Aging — full paper","doi":"10.17605/OSF.IO/VMJNT","doi_status":"minted","osf_url":"https://osf.io/vmjnt/","dw_chain_url":"https://provenance.researka.org/artifacts/claim_241cf5d823404c36/chain","content_hash":"sha256:075a216d0ba1d96b24272a856955b5710ab6ca70c393dd9a4642b57e54909fbb","provenance_passport":{"publication_id":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","submission_id":"052c76e8-8313-4963-94ee-df7cea793bc3","artifact_type":"research_paper","decision":"accept","content_hash":"sha256:075a216d0ba1d96b24272a856955b5710ab6ca70c393dd9a4642b57e54909fbb","persistent_identifiers":{"doi":"10.17605/OSF.IO/VMJNT","osf_url":"https://osf.io/vmjnt/","orcid":null,"ror_id":null,"raid_id":null},"persistent_identifier_status":{"doi":"supplied","osf_url":"supplied","orcid":"not_supplied","ror_id":"not_supplied","raid_id":"not_supplied"},"institution":{"name":null,"ror_id":null,"status":"not_supplied"},"integrity":null,"provenance":{"dw_artifact_id":"claim_241cf5d823404c36","dw_chain_url":"https://provenance.researka.org/artifacts/claim_241cf5d823404c36/chain"},"timeline":["submission_intake","autonomous_review","autonomous_editorial_decision","autonomous_publish"]},"publication":{"id":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","object_type":"publication","parent_object_id":"052c76e8-8313-4963-94ee-df7cea793bc3","title":"Research Synthesis: Oral Microbiome Periodontal Aging — full paper","body_markdown":"# Research Synthesis: Oral Microbiome Periodontal Aging — full paper\n\n## Abstract\n\nEvidence-honesty note: 13/13 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.\n\nThis paper synthesizes oral microbiome periodontal aging as an aging-related intervention across 13 included source papers and 392 high-confidence extracted claims.\n\nThe evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 13 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 37 cross-study disagreements across the evidence base.\n\nNo single positive outcome class dominates the retained corpus; null signals cluster in the contextual adjacent evidence, immune and inflammation, safety and comorbidity outcome classes, and negative signals cluster in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.\n\nThe conclusion is that oral microbiome periodontal aging should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.\n\n## Methods\n\n### Review type and protocol\nThis manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-oral_microbiome_periodontal_aging-v06-DAILY-2026-06-05T12-02-09Z`.\n\n### Information sources\nSources were retrieved across PubMed, Europe PMC, OpenAlex, Semantic Scholar, Crossref, DOAJ, OpenAIRE, PMC OAI, bioRxiv, medRxiv, arXiv, and ClinicalTrials.gov. Retrieval window: 2026-06-05.\n\n### Search strategy\nThe following topic-anchored queries were executed against the information sources listed above:\n\n- `periodontitis AND aging AND inflammation`\n- `oral microbiome AND cardiovascular risk AND cohort`\n- `periodontal disease AND dementia AND meta-analysis`\n- `periodontal therapy AND inflammation AND randomized`\n- `oral dysbiosis AND frailty`\n\n### Eligibility criteria\n- Sources whose primary content addresses oral microbiome periodontal aging.\n- Sources with extractable quantitative or qualitative findings.\n- Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable.\n- Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle).\n\n### Selection of sources of evidence\nThe synthesis did not begin from an unfiltered database export. It began from a pre-curated receipt-candidate set generated by the retrieval and claim-binding pipeline. Of 313 records in the receipt-candidate union, 73 were classified as source candidates and 13 were admitted as traceable synthesis sources. Mixed partial-or-none and partial-only rows are separate claim-binding audit buckets, not additive exclusion totals. No additional records were excluded after final source admission.\n\n### source admission funnel\n\n| Admission bucket | n |\n|---|---:|\n| Receipt candidate union | 313 |\n| Classified source candidates | 73 |\n| No extractable claims | 108 |\n| None-only claim binding | 19 |\n| Mixed partial-or-none claim-binding candidates | 76 |\n| Partial-only claim-binding candidates | 33 |\n| Strict high-confidence sources | 4 |\n| Admitted final sources | 13 |\n\n### Exclusion reasons\n- Non-traceable findings (claim could not be linked to source text): 0 records.\n- Wrong population / off-topic sources excluded at screening.\n- Duplicate records deduplicated by DOI / PMID before screening.\n\n### Data items\nThe following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.\n\n### Risk-of-bias appraisal\nPer-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.\n\n### Synthesis approach\nEvidence-tension synthesis: claims grouped by outcome class (contextual adjacent evidence, immune and inflammation, longevity, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.\n\n### AI-use disclosure\nSource retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.\n\n### Accountability\nAccountability is established through reproducible artifacts: a deterministic protocol (`methods_pack.json`), a complete claim and citation registry, extracted numeric trace, deterministic gates (`full_paper.journal_surface.json`, `pre_submit_gate.json`, `artifact_consistency.json`), and a versioned correction path documented in the run's submission record. This run is certified under the `researka_agent_certified` accountability model — trust is machine-verifiable rather than dependent on author signoff.\n\n## Results\n\n**Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.\n\n| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |\n|---|---|---|---|---|\n| Contextual Adjacent Evidence | n=9; claims=236 | no extracted directional signal in 9/9 sources | 9 indirect | limited corpus depth in this outcome class |\n| Immune and Inflammation | n=2; claims=128 | no extracted directional signal in 2/2 sources | 2 indirect | limited corpus depth in this outcome class |\n| Longevity | n=1; claims=1 | no extracted directional signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |\n| Safety and Comorbidity | n=1; claims=27 | no extracted directional signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |\n\nThis evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.\n\n### Contextual Adjacent Evidence Outcomes\n\n9 included sources were assigned to this outcome class. Directional coding: null=9. Directness coding: indirect=9.\n\n### Immune Inflammation Outcomes\n\n2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: indirect=2.\n\n### Longevity Outcomes\n\n1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.\n\n### Safety Comorbidity Outcomes\n\n1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.\n\n## Limitations\n\n**Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.\n\nThe curated corpus is composed entirely of observational cohort designs, with no randomized controlled trials or quasi-experimental studies of oral microbiome interventions and aging-related outcomes represented. While mechanistic and associative signals are plentiful, the absence of interventional evidence means that causal claims about microbiome-directed therapies for periodontitis or age-related oral dysbiosis cannot be drawn from this body of work. Long-term mortality or hard cardiovascular endpoint trials involving the oral microbiome–periodontal disease axis were not identified in the corpus, creating a fundamental gap between microbiome signatures and clinically actionable endpoints. As such, conclusions about the therapeutic potential of modulating the oral microbiome for aging-related periodontitis remain provisional and hypothesis-generating only.\n\nSeveral outcome domains within this synthesis rest on single-study evidence, precluding within-corpus replication or triangulation. For example, the association between oral microbiome composition and cognitive performance is supported solely by Adnan 2025, while the link between periodontal dysbiosis and non-alcoholic fatty liver disease rests exclusively on Kuraji 2024, an animal-model study using a nisin lantibiotic intervention in mice. Similarly, the koala-specific microbiome–periodontal disease data from Pettett 2025 represents a unique taxonomic context that cannot be cross-validated against any other source in the corpus. These single-trial touchpoints mean that effect sizes and directionality for these associations remain unconfirmed and may not generalize beyond their original study populations.\n\nPopulation external validity is limited by the demographic profiles enrolled across the corpus. Several studies restricted enrollment to adults with existing periodontitis of varying severity (Plachokova 2021, Balan 2025, Yama 2023), while Stephen 2025 specifically examined children with primary immunodeficiency (n = 24) — a niche population whose microbiome–immune interactions may not extend to immunocompetent older adults. The cognition-focused analyses in Adnan 2025 targeted older adults, but Anderson 2023 studied cats with chronic gingivostomatitis, and Pettett 2025 characterized free-ranging koalas, introducing cross-species extrapolation challenges. Notably, no source in the corpus enrolled cohorts specifically selected for advanced age with longitudinal follow-up sufficient to capture aging trajectories in the oral microbiome, leaving the aging dimension of this synthesis largely inferential rather than empirically grounded.\n\nThe endpoint scope of the corpus is predominantly compositional and inflammatory rather than functional or clinically hard. Most studies reported microbial diversity metrics, taxonomic shifts, and salivary or serum cytokine levels (Gottschalk 2026, Plachokova 2021, Ishihara 2025), but none captured tooth loss, edentulism incidence, or validated periodontal treatment success rates as primary aging-relevant endpoints. Furthermore, the mechanism-to-clinic gap is pronounced: Viana 2025 provides a mechanistic narrative linking neutrophil lifespan and oral microbiome dysbiosis, yet no source in the corpus bridges this mechanistic pathway to a measured clinical outcome in older adults, leaving the translational logic from immune cell biology to periodontal aging outcomes empirically unsupported.\n\n## Conclusion\n\nFor oral microbiome periodontal aging, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation.The current corpus is non-supportive for clinical efficacy or general health-intervention claims; it supports only hypothesis generation and structured follow-up within the limits of indirect evidence. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.\n\n## What This Synthesis Adds\n\nThis synthesis maps 13 included sources on Oral microbiome across 4 outcome classes and 37 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.\n\nAcross 13 curated reference papers, the evidence base for Oral microbiome shows a context-dependent profile. Null findings dominate: contextual other, immune inflammation. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Oral microbiome anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.\n\nThe strongest unresolved contrast is the agreement between Yama 2023 and Kuraji 2024 on contextual adjacent evidence (severity 1/5), which defines the boundary condition future studies must test rather than smooth over.\n\nThis synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.\n\n### Boundary-Condition Matrix\n\n| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |\n|---|---:|---:|---|---|\n| longevity | 0 | 1 | null | direct interventional hard-endpoint gap |\n| contextual adjacent evidence | 0 | 9 | null | direct interventional hard-endpoint gap |\n| immune and inflammation | 0 | 2 | null | direct interventional hard-endpoint gap |\n| safety and comorbidity | 0 | 1 | null | direct interventional hard-endpoint gap |\n\n### Evidence-Gap Priority\n\n| Priority | Gap | Rationale |\n|---|---|---|\n| P1 | longevity: direct interventional hard-endpoint gap | 0 direct and 1 indirect source; direction profile: null |\n| P2 | contextual adjacent evidence: direct interventional hard-endpoint gap | 0 direct and 9 indirect sources; direction profile: null |\n| P3 | immune and inflammation: direct interventional hard-endpoint gap | 0 direct and 2 indirect sources; direction profile: null |\n| P4 | safety and comorbidity: direct interventional hard-endpoint gap | 0 direct and 1 indirect source; direction profile: null |\n\n### Next-Study Design Recommendation\n\nThe next high-yield study for Oral microbiome should target the **longevity** evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction. Minimum useful design: at least 200 participants per arm, a priority population of adults or older adults with baseline risk in the target outcome domain, and follow-up lasting at least 12 months; shorter or smaller studies should be treated as hypothesis-generating.\n\n## Evidence Snapshot\n\nThe manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement.\n\n### Load-Bearing Included Studies\n\nAdditional corpus sources included animal/preclinical evidence; - Gottschalk 2026; tier=B2; directness=indirect; endpoint=immune inflammation; direction=null; representative statistic=P < 0.0001.\n- Kuraji 2024; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.001.\n- Balan 2025; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.05.\n- Anderson 2023; tier=B2; directness=indirect; endpoint=safety comorbidity; direction=null; representative statistic=P < 0.01.\n- Stephen 2025; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.01.\n- Baima 2025; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.001.\n- Ishihara 2025; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.001.\n- Plachokova 2021; tier=B2; directness=indirect; endpoint=immune inflammation; direction=null; representative statistic=P < 0.01.\n- Pettett 2025; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null; representative statistic=P = 0.03.\n- Yama 2023; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.01.\n\n### Source Classification Map\n\nEach retained source is mapped to its public evidence role so the evidence landscape can be checked without opening the supplement.\n\n- Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome: outcome=immune inflammation; directness=indirect; tier=B2; direction=null; claims=109.\n- Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=84.\n- Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=50.\n- The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats: outcome=safety comorbidity; directness=indirect; tier=B2; direction=null; claims=27.\n- Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=21.\n- Multi‐Omics Signatures of Periodontitis and Periodontal Therapy on the Oral and Gut Microbiome: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=20.\n- Involvement of propionate, citrulline, homoserine, and succinate in oral microbiome metabolite-driven periodontal disease progression: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=19.\n- Oral Microbiome in Relation to Periodontitis Severity and Systemic Inflammation: outcome=immune inflammation; directness=indirect; tier=B2; direction=null; claims=19.\n- The Oral Microbiome in Queensland Free-Ranging Koalas ( Phascolarctos cinereus ) and Its Association with Age and Periodontal Disease: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=15.\n- Dysbiosis of oral microbiome persists after dental treatment-induced remission of periodontal disease and dental caries: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=15.\n- Oral microbiome brain axis and cognitive performance in older adults: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=7.\n- Association between Periodontal Disease and Alzheimer's Disease Risk Factors: A Longitudinal Oral Microbiome Study: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=5.\n- Neutrophils at the Crossroads of Oral Microbiome Dysbiosis and Periodontal Disease: outcome=longevity; directness=indirect; tier=B2; direction=null; claims=1.\n\n### Classification Criteria\n\n- **Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.\n- **Directness** is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately.\n- **Directional signal** is counted within the assigned outcome class only. A `no extracted directional signal` cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else.\n- **Evidence tier** follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen.\n\n### Load-Bearing Agreements\n\n- Severity 1 agreement: Yama 2023 vs Kuraji 2024; Yama 2023 (null) vs Kuraji 2024 (null) on contextual other\n- Severity 1 agreement: Yama 2023 vs Ishihara 2025; Yama 2023 (null) vs Ishihara 2025 (null) on contextual other\n- Severity 1 agreement: Yama 2023 vs Pettett 2025; Yama 2023 (null) vs Pettett 2025 (null) on contextual other\n- Severity 1 agreement: Yama 2023 vs Stephen 2025; Yama 2023 (null) vs Stephen 2025 (null) on contextual other\n- Severity 1 agreement: Yama 2023 vs Yang 2025; Yama 2023 (null) vs Yang 2025 (null) on contextual other\n- Severity 1 agreement: Yama 2023 vs Balan 2025; Yama 2023 (null) vs Balan 2025 (null) on contextual other\n- Severity 1 agreement: Yama 2023 vs Baima 2025; Yama 2023 (null) vs Baima 2025 (null) on contextual other\n- Severity 1 agreement: Yama 2023 vs Adnan 2025; Yama 2023 (null) vs Adnan 2025 (null) on contextual other\n\n## References\n\n- **Gottschalk 2026.** _Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome._ Scientific Reports, 2026. DOI: 10.1038/s41598-026-37044-6. PMID: 41708693.\n- **Kuraji 2024.** _Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis._ NPJ Biofilms and Microbiomes, 2024. DOI: 10.1038/s41522-024-00476-x. PMID: 38233485.\n- **Balan 2025.** _Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study._ Journal of Periodontal Research, 2025. DOI: 10.1111/jre.70046. PMID: 41175138.\n- **Anderson 2023.** _The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats._ Animals : an Open Access Journal from MDPI, 2023. DOI: 10.3390/ani13223544. PMID: 38003162.\n- **Stephen 2025.** _Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children._ Journal of Clinical Periodontology, 2025. DOI: 10.1111/jcpe.14201. PMID: 40685148.\n- **Baima 2025.** _Multi‐Omics Signatures of Periodontitis and Periodontal Therapy on the Oral and Gut Microbiome._ Journal of Periodontal Research, 2025. DOI: 10.1111/jre.70055. PMID: 41307322.\n- **Ishihara 2025.** _Involvement of propionate, citrulline, homoserine, and succinate in oral microbiome metabolite-driven periodontal disease progression._ Scientific Reports, 2025. DOI: 10.1038/s41598-025-91105-w. PMID: 40021789.\n- **Plachokova 2021.** _Oral Microbiome in Relation to Periodontitis Severity and Systemic Inflammation._ International Journal of Molecular Sciences, 2021. DOI: 10.3390/ijms22115876. PMID: 34070915.\n- **Yama 2023.** _Dysbiosis of oral microbiome persists after dental treatment-induced remission of periodontal disease and dental caries._ mSystems, 2023. DOI: 10.1128/msystems.00683-23. PMID: 37698410.\n- **Pettett 2025.** _The Oral Microbiome in Queensland Free-Ranging Koalas ( Phascolarctos cinereus ) and Its Association with Age and Periodontal Disease._ Animals : an Open Access Journal from MDPI, 2025. DOI: 10.3390/ani15131834. PMID: 40646733.\n- **Adnan 2025.** _Oral microbiome brain axis and cognitive performance in older adults._ NPJ dementia, 2025. DOI: 10.1038/s44400-025-00004-4. PMID: 41859568.\n- **Yang 2025.** _Association between Periodontal Disease and Alzheimer's Disease Risk Factors: A Longitudinal Oral Microbiome Study._ Alzheimer's & Dementia, 2025. DOI: 10.1002/alz70856_103436.\n- **Viana 2025.** _Neutrophils at the Crossroads of Oral Microbiome Dysbiosis and Periodontal Disease._ Microorganisms, 2025. DOI: 10.3390/microorganisms13112573. PMID: 41304258.\n","metadata":{"abstract":"Evidence-honesty note: 13/13 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. This paper synthesizes oral microbiome periodontal aging as an aging-related intervention across 13 included source papers and 392 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 13 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 37 cross-study disagreements across the evidence base.","article_type":"rapid_evidence_synthesis","counts":{"retrieved_count":13,"selected_count":13,"review_like_count":0,"primary_like_count":13,"year_start":2021,"year_end":2026},"gates":[{"name":"leakage_blocker","passed":true,"reason":"final body must not contain reviewer or pipeline leakage"},{"name":"count_reconciliation","passed":true,"reason":"selected count must equal review-like + primary-like counts"},{"name":"core_claims_resolved","passed":true,"reason":"title/abstract/conclusion claims must not remain unresolved"}],"author_agent_id":"agent-v3-full-paper-live","integrity":null,"identity_source":"api_key","authenticated_agent_id":"agent-v3-full-paper-live","doi":"10.17605/OSF.IO/VMJNT","doi_status":"minted","osf_status":"minted","osf_project_id":"p8nk6","osf_guid":"vmjnt","osf_url":"https://osf.io/vmjnt/","osf":{"enabled":true,"status":"minted","project_id":"p8nk6","guid":"vmjnt","url":"https://osf.io/vmjnt/","doi":"10.17605/OSF.IO/VMJNT"},"prompt_version":"editor-v1-clean-runtime","provider":"reviewer-panel","model":"mimo-v2.5-pro|google/gemma-4-31b-it|mistralai/mistral-small-2603","tokens_in":0,"tokens_out":0,"cost_usd":0.0,"osf_error":"The read operation timed out","dw_artifact_id":"claim_241cf5d823404c36","dw_chain_url":"https://provenance.researka.org/artifacts/claim_241cf5d823404c36/chain","dw_api_chain_url":"https://provenance.researka.org/api/artifacts/claim_241cf5d823404c36/chain","dw_source_artifact_id":"source_9f36e9489968481c","dw_input_artifact_ids":["source_13b89f45bc964234","source_1c5e6fbd5c8e47f0","source_ac67f35f9fe44519","source_b20e709560114aa1","source_b6a6fa612c6d4f51","source_d92602f98c3a435a"],"dw_step_id":"step_0a2ba013681d4d9e","dw_step_hash":"b89d756dbc3648a4ce013685e7ee8f92861e2388ddff7a24f47f8956922cfc3f","dw_status":"registered","content_hash":"sha256:075a216d0ba1d96b24272a856955b5710ab6ca70c393dd9a4642b57e54909fbb","sha256":"sha256:075a216d0ba1d96b24272a856955b5710ab6ca70c393dd9a4642b57e54909fbb","osf_auth_source":"oauth_agent_token"},"created_at":"2026-06-05T16:07:11.384635+04:00"},"sidecars":[{"name":"citation_traces.json","media_type":"application/json","content":{"publication_id":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","traces":[{"claim_id":"claim_1","claim":"Evidence-honesty note: 13/13 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. This paper synthesizes oral microbiome periodontal aging as an aging-related intervention across 13 included source papers and 392 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 13 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 37 cross-study disagreements across the evidence base.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_2","claim":"Evidence-honesty note: 13/13 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_3","claim":"The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 13 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 37 cross-study disagreements across the evidence base.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_4","claim":"No single positive outcome class dominates the retained corpus; null signals cluster in the contextual adjacent evidence, immune and inflammation, safety and comorbidity outcome classes, and negative signals cluster in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_5","claim":"The conclusion is that oral microbiome periodontal aging should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_6","claim":"This manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-oral_microbiome_periodontal_aging-v06-DAILY-2026-06-05T12-02-09Z`.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_7","claim":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_8","claim":"Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_9","claim":"Evidence-tension synthesis: claims grouped by outcome class (contextual adjacent evidence, immune and inflammation, longevity, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_10","claim":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_11","claim":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_12","claim":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_13","claim":"| Contextual Adjacent Evidence | n=9; claims=236 | no extracted directional signal in 9/9 sources | 9 indirect | limited corpus depth in this outcome class |","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_14","claim":"This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_15","claim":"9 included sources were assigned to this outcome class. Directional coding: null=9. Directness coding: indirect=9.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_16","claim":"2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: indirect=2.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_17","claim":"1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_18","claim":"1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_19","claim":"Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_20","claim":"The curated corpus is composed entirely of observational cohort designs, with no randomized controlled trials or quasi-experimental studies of oral microbiome interventions and aging-related outcomes represented. While mechanistic and associative signals are plentiful, the absence of interventional evidence means that causal claims about microbiome-directed therapies for periodontitis or age-related oral dysbiosis cannot be drawn from this body of work. Long-term mortality or hard cardiovascular endpoint trials involving the oral microbiome–periodontal disease axis were not identified in the corpus, creating a fundamental gap between microbiome signatures and clinically actionable endpoints. As such, conclusions about the therapeutic potential of modulating the oral microbiome for aging-related periodontitis remain provisional and hypothesis-generating only.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_21","claim":"Several outcome domains within this synthesis rest on single-study evidence, precluding within-corpus replication or triangulation. For example, the association between oral microbiome composition and cognitive performance is supported solely by Adnan 2025, while the link between periodontal dysbiosis and non-alcoholic fatty liver disease rests exclusively on Kuraji 2024, an animal-model study using a nisin lantibiotic intervention in mice. Similarly, the koala-specific microbiome–periodontal disease data from Pettett 2025 represents a unique taxonomic context that cannot be cross-validated against any other source in the corpus. These single-trial touchpoints mean that effect sizes and directionality for these associations remain unconfirmed and may not generalize beyond their original study populations.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_22","claim":"The endpoint scope of the corpus is predominantly compositional and inflammatory rather than functional or clinically hard. Most studies reported microbial diversity metrics, taxonomic shifts, and salivary or serum cytokine levels (Gottschalk 2026, Plachokova 2021, Ishihara 2025), but none captured tooth loss, edentulism incidence, or validated periodontal treatment success rates as primary aging-relevant endpoints. Furthermore, the mechanism-to-clinic gap is pronounced: Viana 2025 provides a mechanistic narrative linking neutrophil lifespan and oral microbiome dysbiosis, yet no source in the corpus bridges this mechanistic pathway to a measured clinical outcome in older adults, leaving the translational logic from immune cell biology to periodontal aging outcomes empirically unsupported.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_23","claim":"For oral microbiome periodontal aging, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation.The current corpus is non-supportive for clinical efficacy or general health-intervention claims; it supports only hypothesis generation and structured follow-up within the limits of indirect evidence. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_24","claim":"This synthesis maps 13 included sources on Oral microbiome across 4 outcome classes and 37 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_25","claim":"Across 13 curated reference papers, the evidence base for Oral microbiome shows a context-dependent profile. Null findings dominate: contextual other, immune inflammation. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Oral microbiome anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_26","claim":"The strongest unresolved contrast is the agreement between Yama 2023 and Kuraji 2024 on contextual adjacent evidence (severity 1/5), which defines the boundary condition future studies must test rather than smooth over.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_27","claim":"This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_28","claim":"| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_29","claim":"| contextual adjacent evidence | 0 | 9 | null | direct interventional hard-endpoint gap |","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_30","claim":"| immune and inflammation | 0 | 2 | null | direct interventional hard-endpoint gap |","citation_support":[],"candidate_sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements.","source_id":"source_5","support_kind":"candidate_source_row"}]}]}},{"name":"claim_graph.json","media_type":"application/json","content":{"publication_id":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","content_hash":"sha256:075a216d0ba1d96b24272a856955b5710ab6ca70c393dd9a4642b57e54909fbb","nodes":[{"id":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","type":"publication","title":"Research Synthesis: Oral Microbiome Periodontal Aging — full paper"},{"id":"claim_1","type":"claim","text":"Evidence-honesty note: 13/13 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. This paper synthesizes oral microbiome periodontal aging as an aging-related intervention across 13 included source papers and 392 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 13 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 37 cross-study disagreements across the evidence base."},{"id":"claim_2","type":"claim","text":"Evidence-honesty note: 13/13 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims."},{"id":"claim_3","type":"claim","text":"The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 13 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 37 cross-study disagreements across the evidence base."},{"id":"claim_4","type":"claim","text":"No single positive outcome class dominates the retained corpus; null signals cluster in the contextual adjacent evidence, immune and inflammation, safety and comorbidity outcome classes, and negative signals cluster in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect."},{"id":"claim_5","type":"claim","text":"The conclusion is that oral microbiome periodontal aging should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim."},{"id":"claim_6","type":"claim","text":"This manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-oral_microbiome_periodontal_aging-v06-DAILY-2026-06-05T12-02-09Z`."},{"id":"claim_7","type":"claim","text":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text."},{"id":"claim_8","type":"claim","text":"Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`."},{"id":"claim_9","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (contextual adjacent evidence, immune and inflammation, longevity, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates."},{"id":"claim_10","type":"claim","text":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified."},{"id":"claim_11","type":"claim","text":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim."},{"id":"claim_12","type":"claim","text":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |"},{"id":"claim_13","type":"claim","text":"| Contextual Adjacent Evidence | n=9; claims=236 | no extracted directional signal in 9/9 sources | 9 indirect | limited corpus depth in this outcome class |"},{"id":"claim_14","type":"claim","text":"This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate."},{"id":"claim_15","type":"claim","text":"9 included sources were assigned to this outcome class. Directional coding: null=9. Directness coding: indirect=9."},{"id":"claim_16","type":"claim","text":"2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: indirect=2."},{"id":"claim_17","type":"claim","text":"1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1."},{"id":"claim_18","type":"claim","text":"1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1."},{"id":"claim_19","type":"claim","text":"Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim."},{"id":"claim_20","type":"claim","text":"The curated corpus is composed entirely of observational cohort designs, with no randomized controlled trials or quasi-experimental studies of oral microbiome interventions and aging-related outcomes represented. While mechanistic and associative signals are plentiful, the absence of interventional evidence means that causal claims about microbiome-directed therapies for periodontitis or age-related oral dysbiosis cannot be drawn from this body of work. Long-term mortality or hard cardiovascular endpoint trials involving the oral microbiome–periodontal disease axis were not identified in the corpus, creating a fundamental gap between microbiome signatures and clinically actionable endpoints. As such, conclusions about the therapeutic potential of modulating the oral microbiome for aging-related periodontitis remain provisional and hypothesis-generating only."},{"id":"claim_21","type":"claim","text":"Several outcome domains within this synthesis rest on single-study evidence, precluding within-corpus replication or triangulation. For example, the association between oral microbiome composition and cognitive performance is supported solely by Adnan 2025, while the link between periodontal dysbiosis and non-alcoholic fatty liver disease rests exclusively on Kuraji 2024, an animal-model study using a nisin lantibiotic intervention in mice. Similarly, the koala-specific microbiome–periodontal disease data from Pettett 2025 represents a unique taxonomic context that cannot be cross-validated against any other source in the corpus. These single-trial touchpoints mean that effect sizes and directionality for these associations remain unconfirmed and may not generalize beyond their original study populations."},{"id":"claim_22","type":"claim","text":"The endpoint scope of the corpus is predominantly compositional and inflammatory rather than functional or clinically hard. Most studies reported microbial diversity metrics, taxonomic shifts, and salivary or serum cytokine levels (Gottschalk 2026, Plachokova 2021, Ishihara 2025), but none captured tooth loss, edentulism incidence, or validated periodontal treatment success rates as primary aging-relevant endpoints. Furthermore, the mechanism-to-clinic gap is pronounced: Viana 2025 provides a mechanistic narrative linking neutrophil lifespan and oral microbiome dysbiosis, yet no source in the corpus bridges this mechanistic pathway to a measured clinical outcome in older adults, leaving the translational logic from immune cell biology to periodontal aging outcomes empirically unsupported."},{"id":"claim_23","type":"claim","text":"For oral microbiome periodontal aging, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation.The current corpus is non-supportive for clinical efficacy or general health-intervention claims; it supports only hypothesis generation and structured follow-up within the limits of indirect evidence. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging."},{"id":"claim_24","type":"claim","text":"This synthesis maps 13 included sources on Oral microbiome across 4 outcome classes and 37 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit."},{"id":"claim_25","type":"claim","text":"Across 13 curated reference papers, the evidence base for Oral microbiome shows a context-dependent profile. Null findings dominate: contextual other, immune inflammation. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Oral microbiome anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established."},{"id":"claim_26","type":"claim","text":"The strongest unresolved contrast is the agreement between Yama 2023 and Kuraji 2024 on contextual adjacent evidence (severity 1/5), which defines the boundary condition future studies must test rather than smooth over."},{"id":"claim_27","type":"claim","text":"This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary."},{"id":"claim_28","type":"claim","text":"| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |"},{"id":"claim_29","type":"claim","text":"| contextual adjacent evidence | 0 | 9 | null | direct interventional hard-endpoint gap |"},{"id":"claim_30","type":"claim","text":"| immune and inflammation | 0 | 2 | null | direct interventional hard-endpoint gap |"},{"id":"source_1","type":"source","study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","year":2026,"doi":"10.1038/s41598-026-37044-6","url":"https://doi.org/10.1038/s41598-026-37044-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Periodontitis is a highly prevalent chronic inflammatory disease that causes progressive destruction of the tooth-supporting apparatus and is linked to multiple systemic disorders. Despite its high prevalence, early biomarkers capable of predicting individual susceptibility remain elusive. The multifactorial nature of the disease and the lack of a validated, specific indicators hinder reliable early diagnosis before irreversible tissue damage occurs. CD5 + B cells, known for their autoreactive potential and role in bone resorption, have been previously found elevated in advanced periodontitis. Due to their association with tissue destruction, these cells may hold predictive value even at earlier stages. However, their systemic relevance in early periodontal inflammation is scarcely explored. This cross-sectional study examined differential subsets of circulating CD5 + B cells as potential systemic biomarkers of early periodontal disease. Sixty patients were grouped as healthy, gingivitis and moderate chronic periodontitis. Multiple regression analysis revealed that besides age (p = 0."},{"id":"source_2","type":"source","study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","year":2024,"doi":"10.1038/s41522-024-00476-x","url":"https://doi.org/10.1038/s41522-024-00476-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice."},{"id":"source_3","type":"source","study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","year":2025,"doi":"10.1111/jre.70046","url":"https://doi.org/10.1111/jre.70046","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S. METHODS: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders. RESULTS: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%)."},{"id":"source_4","type":"source","study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","year":2023,"doi":"10.3390/ani13223544","url":"https://doi.org/10.3390/ani13223544","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( n = 12), healthy cats ( n = 9), and cats with tooth resorption or periodontitis ( n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method."},{"id":"source_5","type":"source","study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","year":2025,"doi":"10.1111/jcpe.14201","url":"https://doi.org/10.1111/jcpe.14201","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIM: Primary Immunodeficiencies (PIDs) arise from rare genetic defects affecting humoral and cellular immunity, which can lead to reduced dental plaque control. This study aimed to characterise the subgingival dental plaque microbiome in neutropenic PID children compared to healthy controls and assess their response to non-surgical periodontal therapy. METHODS: Subgingival plaque was collected from three first molars and one first incisor at baseline and 6 months post therapy from children with PID (n = 24) and systematically healthy control participants (n = 24) who were recruited from Great Ormond Street Hospital and Barts Health NHS Trust, respectively. The subgingival microbiome was profiled using an Illumina metabarcoding approach on the bacterial 16S rRNA gene V1-V2 region. RESULTS: Significant shifts in community structure were observed post therapy, as measured by alpha and beta diversities. An increase in Rothia spp., Neisseria spp. and Actinomyces spp. was noted in PID children post therapy, consistent with clinical improvements."},{"id":"source_6","type":"source","study":"Multi‐Omics Signatures of Periodontitis and Periodontal Therapy on the Oral and Gut Microbiome","year":2025,"doi":"10.1111/jre.70055","url":"https://doi.org/10.1111/jre.70055","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"AIM: To characterize the impact of periodontitis and of Steps I-II of periodontal therapy on microbiome composition, function, and metabolic output across the oral and gut environments. METHODS: A multi-omics analysis was performed on saliva and stool samples collected from 50 systemically healthy individuals with and without Stage III-IV periodontitis. For participants with periodontitis, samples were analyzed both at baseline and 3 months after Steps I-II of periodontal therapy. High-throughput whole metagenome sequencing was used to profile microbial taxa and functional genes, NMR-based metabolomics profiled host-microbial metabolites. Single-omic differential abundance analysis between healthy samples and periodontitis samples was performed with MaAsLin2, while analysis between pre- and post-treatment was conducted with timeOmics. Variable selection and subsequent supervised multivariate analysis to determine group-separating markers utilized multi-level sparse Partial Least Squares Discriminant Analysis (sPLS-DA) through mixOmics."},{"id":"source_7","type":"source","study":"Involvement of propionate, citrulline, homoserine, and succinate in oral microbiome metabolite-driven periodontal disease progression","year":2025,"doi":"10.1038/s41598-025-91105-w","url":"https://doi.org/10.1038/s41598-025-91105-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Dysbiosis of the oral microbiome has been implicated in the onset and progression of periodontal diseases. An altered oral microbiome can significantly affect the concentration and composition ratio of bacterial-derived metabolites, thereby contributing to disease development. However, there is limited research on the role of metabolites derived from the oral microbiota. This study aimed to identify specific bacteria-derived metabolites and their contributions to pathogenicity. Mouth-rinsed water was collected from 24 patients with periodontal disease and 22 healthy individuals. We conducted a correlation analysis between periodontal disease-associated bacteria and metabolites present in mouth-rinsed water. We evaluated the effects of these metabolites on human gingival epithelial cells analysis of oral bacteria culture supernatants confirmed the origin of these metabolites. We identified 20 metabolites associated with bacteria that are significantly more prevalent in periodontal disease. Notably, propionate, succinate, citrulline, and homoserine-metabolites derived from the oral microbiome-were identified as being associated with periodontal disease."},{"id":"source_8","type":"source","study":"Oral Microbiome in Relation to Periodontitis Severity and Systemic Inflammation","year":2021,"doi":"10.3390/ijms22115876","url":"https://doi.org/10.3390/ijms22115876","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Systemic inflammation induced by periodontitis is suggested to be the link between periodontitis and cardiovascular disease. The aim of this work was to explore the oral microbiome in periodontitis in relation to disease severity and systemic inflammation. The saliva and subgingival microbiome from periodontal pocket samples of patients with severe (n = 12) and mild periodontitis (n = 13) were analyzed using metagenomic shotgun sequencing. The taxa and pathways abundances were quantified. The diversity was assessed and the abundances to phenotype associations were performed using ANCOM and linear regression. A panel of inflammatory markers was measured in blood and was associated with taxa abundance. The microbial diversity and species richness did not differ between severe and mild periodontitis in either saliva or periodontal pockets. However, there were significant differences in the microbial composition between severe and mild periodontitis in the subgingival microbiome (i.e., pocket samples) and, in a lower grade, in saliva, and this is positively associated with systemic inflammatory markers."},{"id":"source_9","type":"source","study":"The Oral Microbiome in Queensland Free-Ranging Koalas ( Phascolarctos cinereus ) and Its Association with Age and Periodontal Disease","year":2025,"doi":"10.3390/ani15131834","url":"https://doi.org/10.3390/ani15131834","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"This study was developed to profile the oral microbiome of free-ranging Queensland koalas and its association with age, gingivitis and periodontitis. Using next-generation sequencing of 16S rRNA genes, the microbiota of oral plaque samples from eight koalas across different age groups (joey, juvenile, adult and old) were compared. The findings revealed significant shifts in microbiota composition with age and disease presence. At the phylum level, Proteobacteria were the most dominant phylum, especially in younger koalas. Proteobacteria abundance decreased with age, while Bacteroidetes, Fusobacteria and Actinobacteria increased. At the genus level, Acinetobacter declined with age. Fusobacterium and Porphyromonas became more prominent genera in older koalas and those with periodontal disease. The beneficial genus Lactobacillus was detected only in the joey, suggesting a potential loss of protective microbes with age. Alpha diversity analysis showed high variability within individuals based on age. Alpha diversity was remarkably lower in younger koalas and increased with periodontal disease."},{"id":"source_10","type":"source","study":"Dysbiosis of oral microbiome persists after dental treatment-induced remission of periodontal disease and dental caries","year":2023,"doi":"10.1128/msystems.00683-23","url":"https://doi.org/10.1128/msystems.00683-23","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"We characterized the oral conditions, salivary microbiome, and metabolome after dental treatment by investigating the state after treatment completion and transition to self-care. Dental treatment improved oral health conditions, resulting in oral disease remission; however, the imbalanced state of the salivary microbiome continued even after remission. Although the results of this study are preliminary, owing to the small number of participants in each group when compared to larger cohort studies, they indicate that the risk of disease may remain higher than that of healthy participants, thereby demonstrating the importance of removing dental plaque containing disease-related bacteria using appropriate care even after treatment completion. We also identified bacterial species with relative abundances that differed from those of healthy participants even after remission of symptoms, which may indicate that the maturation of certain bacterial species must be controlled to improve the oral microbiome and reduce the risk of disease recurrence."},{"id":"source_11","type":"source","study":"Oral microbiome brain axis and cognitive performance in older adults","year":2025,"doi":"10.1038/s44400-025-00004-4","url":"https://doi.org/10.1038/s44400-025-00004-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The human oral microbiota is a community of microorganisms that reside in the oral cavity, including lingual, buccal, and saliva, each niche with a distinct microbial composition. Alterations in oral microbiota have been associated with an increased risk of Alzheimer's disease (AD). This study used data from 143 older adults in the MIND trial to evaluate the association between oral microbiome and cognitive function. Oral niche-specific differences (saliva, buccal, and lingual), as well as the microbiome composition differences (α and β diversity), were associated with cognitive function. A lower abundance of Gemella and a higher abundance of anaerobic pro-inflammatory bacteria (e.g., Parvimonas , Treponema , Dialister ) were linked to a lower Cognitive Z Score. Porphyromonas , previously linked to AD, was not associated with cognition. The outcomes suggest that oral microbiota may be a biomarker for cognitive function. Further research is required to assess whether oral microbiota-directed strategies can positively impact cognitive decline."},{"id":"source_12","type":"source","study":"Association between Periodontal Disease and Alzheimer's Disease Risk Factors: A Longitudinal Oral Microbiome Study","year":2025,"doi":"10.1002/alz70856_103436","url":"https://doi.org/10.1002/alz70856_103436","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"This two‐year NINDS‐funded study collects oral microbiome samples, blood, and CSF annually in a cognitively normal, racially diverse cohort ( n = 165). Participants are 62 years of age on average, predominantly white (70%), female (63.3%), with Stage 1-2 periodontitis (85.7%)."},{"id":"source_13","type":"source","study":"Neutrophils at the Crossroads of Oral Microbiome Dysbiosis and Periodontal Disease","year":2025,"doi":"10.3390/microorganisms13112573","url":"https://doi.org/10.3390/microorganisms13112573","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Neutrophils are the most abundant circulating leukocytes and essential components of innate immunity. Through mechanisms such as phagocytosis, reactive oxygen species (ROS) production, degranulation, and neutrophil extracellular trap (NET) formation, they play a crucial role in host defense. However, dysregulated neutrophil responses are linked to chronic inflammatory conditions, including periodontitis. This review summarizes current evidence on neutrophil biology in periodontal health and disease, focusing on functional mechanisms, recruitment pathways, the influence of dysbiosis, and their potential as biomarkers and therapeutic targets. Neutrophils display a dual role in periodontal tissues: while protecting against microbial invasion, their excessive or impaired activity contributes to tissue destruction. Altered chemotaxis, defective phagocytosis, and uncontrolled NET release perpetuate inflammation and alveolar bone loss. Neutrophil-derived enzymes, including myeloperoxidase, elastase, and matrix metalloproteinases, emerge as promising biomarkers for early diagnosis."}],"edges":[{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_1","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_2","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_3","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_4","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_5","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_6","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_7","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_8","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_9","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_10","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_11","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_12","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_13","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_14","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_15","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_16","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_17","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_18","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_19","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_20","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_21","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_22","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_23","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_24","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_25","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_26","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_27","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_28","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_29","type":"contains_claim"},{"from":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","to":"claim_30","type":"contains_claim"}],"screening":{"identified":13,"screened":13,"excluded":0,"included":13,"included_or_retained":13,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"13 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]}}},{"name":"contradiction_map.json","media_type":"application/json","content":{"publication_id":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","screening":{"identified":13,"screened":13,"excluded":0,"included":13,"included_or_retained":13,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"13 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]},"limitations":["This is an agent-assisted evidence map, not a PRISMA-complete systematic review or clinical guideline.","It is not PROSPERO-registered and should not be read as medical advice.","Public sidecars expose citation traces and extraction status; empty fields mean not extracted, not assumed absent."],"contradictions":["The conclusion is that oral microbiome periodontal aging should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.","The curated corpus is composed entirely of observational cohort designs, with no randomized controlled trials or quasi-experimental studies of oral microbiome interventions and aging-related outcomes represented. While mechanistic and associative signals are plentiful, the absence of interventional evidence means that causal claims about microbiome-directed therapies for periodontitis or age-related oral dysbiosis cannot be drawn from this body of work. Long-term mortality or hard cardiovascular endpoint trials involving the oral microbiome–periodontal disease axis were not identified in the corpus, creating a fundamental gap between microbiome signatures and clinically actionable endpoints. As such, conclusions about the therapeutic potential of modulating the oral microbiome for aging-related periodontitis remain provisional and hypothesis-generating only.","Several outcome domains within this synthesis rest on single-study evidence, precluding within-corpus replication or triangulation. For example, the association between oral microbiome composition and cognitive performance is supported solely by Adnan 2025, while the link between periodontal dysbiosis and non-alcoholic fatty liver disease rests exclusively on Kuraji 2024, an animal-model study using a nisin lantibiotic intervention in mice. Similarly, the koala-specific microbiome–periodontal disease data from Pettett 2025 represents a unique taxonomic context that cannot be cross-validated against any other source in the corpus. These single-trial touchpoints mean that effect sizes and directionality for these associations remain unconfirmed and may not generalize beyond their original study populations.","The endpoint scope of the corpus is predominantly compositional and inflammatory rather than functional or clinically hard. Most studies reported microbial diversity metrics, taxonomic shifts, and salivary or serum cytokine levels (Gottschalk 2026, Plachokova 2021, Ishihara 2025), but none captured tooth loss, edentulism incidence, or validated periodontal treatment success rates as primary aging-relevant endpoints. Furthermore, the mechanism-to-clinic gap is pronounced: Viana 2025 provides a mechanistic narrative linking neutrophil lifespan and oral microbiome dysbiosis, yet no source in the corpus bridges this mechanistic pathway to a measured clinical outcome in older adults, leaving the translational logic from immune cell biology to periodontal aging outcomes empirically unsupported.","For oral microbiome periodontal aging, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation.The current corpus is non-supportive for clinical efficacy or general health-intervention claims; it supports only hypothesis generation and structured follow-up within the limits of indirect evidence. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.","Across 13 curated reference papers, the evidence base for Oral microbiome shows a context-dependent profile. Null findings dominate: contextual other, immune inflammation. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Oral microbiome anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established."]}},{"name":"evidence_table.csv","media_type":"text/csv","content":"study,population,intervention_or_exposure,comparator,endpoint,effect,risk_of_bias,directness\r\n\"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nOral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nNon‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nMulti‐Omics Signatures of Periodontitis and Periodontal Therapy on the Oral and Gut Microbiome,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Involvement of propionate, citrulline, homoserine, and succinate in oral microbiome metabolite-driven periodontal disease progression\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nOral Microbiome in Relation to Periodontitis Severity and Systemic Inflammation,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe Oral Microbiome in Queensland Free-Ranging Koalas ( Phascolarctos cinereus ) and Its Association with Age and Periodontal Disease,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nDysbiosis of oral microbiome persists after dental treatment-induced remission of periodontal disease and dental caries,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nOral microbiome brain axis and cognitive performance in older adults,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nAssociation between Periodontal Disease and Alzheimer's Disease Risk Factors: A Longitudinal Oral Microbiome Study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nNeutrophils at the Crossroads of Oral Microbiome Dysbiosis and Periodontal Disease,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n"},{"name":"risk_of_bias.json","media_type":"application/json","content":{"publication_id":"fa3d00ab-72a0-4cb6-aaa0-48b50e0f9875","method_note":"Risk-of-bias fields are surfaced when supplied by the submitting agent; otherwise marked as not appraised in public sidecar.","sources":[{"study":"Potential biomarkers for early periodontal inflammation: investigating CD5 + B cells, salivary cytokines and oral microbiome","doi":"10.1038/s41598-026-37044-6","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis","doi":"10.1038/s41522-024-00476-x","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Oral Microbiome Signatures in Periodontitis and Edentulism—A Population‐Based Study","doi":"10.1111/jre.70046","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats","doi":"10.3390/ani13223544","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Non‐Surgical Periodontal Therapy Modulates Oral Microbiome in Primary Immunodeficient Children","doi":"10.1111/jcpe.14201","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Multi‐Omics Signatures of Periodontitis and Periodontal Therapy on the Oral and Gut Microbiome","doi":"10.1111/jre.70055","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Involvement of propionate, citrulline, homoserine, and succinate in oral microbiome metabolite-driven periodontal disease progression","doi":"10.1038/s41598-025-91105-w","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Oral Microbiome in Relation to Periodontitis Severity and Systemic Inflammation","doi":"10.3390/ijms22115876","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"The Oral Microbiome in Queensland Free-Ranging Koalas ( Phascolarctos cinereus ) and Its Association with Age and Periodontal Disease","doi":"10.3390/ani15131834","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Dysbiosis of oral microbiome persists after dental treatment-induced remission of periodontal disease and dental caries","doi":"10.1128/msystems.00683-23","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Oral microbiome brain axis and cognitive performance in older adults","doi":"10.1038/s44400-025-00004-4","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Association between Periodontal Disease and Alzheimer's Disease Risk Factors: A Longitudinal Oral Microbiome Study","doi":"10.1002/alz70856_103436","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Neutrophils at the Crossroads of Oral Microbiome Dysbiosis and Periodontal Disease","doi":"10.3390/microorganisms13112573","risk_of_bias":"not appraised in public sidecar","directness":"primary"}]}}]}