Oral microbiome–host axis in endometriosis: systematic review of Fusobacterium nucleatum
Current evidence does not support a consistent or causal association between F. nucleatum and endometriosis; the two direct tissue studies are conflicting and all human evidence is of very low certainty.
| Population | Women with confirmed endometriosis (surgical or histological diagnosis); animal models of experimental endometriosis |
|---|---|
| Intervention | Presence/abundance of Fusobacterium nucleatum or F. nucleatum-complex taxa in endometrial tissue, oral, vaginal, or peritoneal microbiome samples |
| Comparator | Women without endometriosis (healthy controls or without pelvic pain) or non-induced animals |
| Outcome | Fusobacterium positivity in endometrial tissue (cases vs. controls); Oral Fusobacterium abundance by endometriosis stage; Vaginal F. animalis depletion in chronic pelvic pain with endometriosis; TGF-β-mediated endometriotic lesion growth (animal model); F. nucleatum-associated fibrosis in endometriotic lesions (experimental) |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| Fusobacterium positivity in endometrial tissue (cases vs. controls) | Muraoka et al.: 64.3% vs 7.1% (n=42 vs 42), in the IC reported; Graciano-Espana et al.: in the significant difference (n=55 vs 37), in the effect size reported | — | Low | — | 2 studies |
| Oral Fusobacterium abundance by endometriosis stage | Enrichment in moderate/severe endometriosis reported qualitatively; in the quantitative effect size or IC provided | — | Low | — | 1 studies |
| Vaginal F. animalis depletion in chronic pelvic pain with endometriosis | Depletion reported qualitatively; in the quantitative effect size or IC provided | — | Low | — | 1 studies |
| TGF-β-mediated endometriotic lesion growth (animal model) | Single translational study; in the pooled effect size; in the IC reported; in the independent replication | — | Very low | — | 1 studies |
| F. nucleatum-associated fibrosis in endometriotic lesions (experimental) | Single translational study; in the quantitative pooled effect; in the IC; in the independent replication | — | Very low | — | 1 studies |
Context
Endometriosis affects ~190 million women and its pathogenesis remains incompletely understood. The oral-to-pelvic microbial translocation hypothesis attracted attention after reports of F. nucleatum in endometrial lesions, but data consistency was unknown. This review synthesises available evidence before it informs clinical practice or therapeutic research.
What the study showed
Four human studies (384 participants at study level) were included. Muraoka et al. detected Fusobacterium in 64.3% (27/42) of endometrial samples from cases versus 7.1% (3/42) of controls; Graciano-España et al. found no significant difference in F. nucleatum abundance between 55 cases and 37 controls. Indirect microbiome studies reported oral Fusobacterium enrichment in moderate/severe endometriosis and vaginal F. animalis depletion in chronic pelvic pain with endometriosis. Experimental evidence of TGF-β-mediated lesion growth and fibrosis derives from a single translational study without independent replication.
How it was done
Systematic review following PRISMA 2020; PubMed/MEDLINE, Embase, Web of Science, and Google Scholar searched through August 31, 2026. Risk of bias assessed using adapted ROBINS-I (human observational studies) and SYRCLE (animal studies). Meta-analysis was deemed inappropriate due to substantial heterogeneity in anatomical compartments, detection methods, and outcomes; qualitative synthesis was performed.
Effect magnitude
No pooled effect size is available; findings are qualitative. The only comparable quantitative datum is from Muraoka et al.: 64.3% vs. 7.1% positivity in a 42×42 subset, without a reported 95% CI in the review. This finding is unreplicated and conflicts with the subsequent study.
Risk of bias
All human studies were rated at serious overall risk of bias (ROBINS-I); GRADE certainty is very low. Heterogeneity in sampled anatomical compartments, detection methods (PCR, 16S sequencing, culture), and case definitions precludes quantitative synthesis. Non-standardised contamination control and absence of anatomical site pairing undermine internal validity. Animal studies assessed by SYRCLE lack independent replication.
What this study does NOT prove
This review does not prove causality, oral-to-pelvic microbial translocation, or efficacy of any antimicrobial intervention. Findings are not generalisable beyond the populations studied (predominantly Asian and Latin American) and do not confirm F. nucleatum as a therapeutic target.
In clinical practice
There is no basis for recommending F. nucleatum screening, oral microbiome intervention, or antimicrobial therapy in endometriosis patients. Diagnosis and management follow established guidelines. Clinicians may inform patients that a role for F. nucleatum is biologically plausible but unproven.
Limitations
All human studies were rated at serious overall risk of bias (ROBINS-I); GRADE certainty is very low. Heterogeneity in sampled anatomical compartments, detection methods (PCR, 16S sequencing, culture), and case definitions precludes quantitative synthesis. Non-standardised contamination control and absence of anatomical site pairing undermine internal validity. Animal studies assessed by SYRCLE lack independent replication.
What is still missing
Case-control studies with paired multi-site anatomical sampling, rigorous contamination control, strain-level analysis, and longitudinal designs are needed to establish temporality and causality.
Technical appendix
Version history
- 1.0 · 2026-11-03 — Auto-generated under Evidence Standard v1.0