The emerging oral microbe-host axis in endometriosis: a systematic review of Fusobacterium nucleatum

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Abstract
Background: Fusobacterium nucleatum , an oral-associated bacterium implicated in several extraoral diseases, has recently been proposed as a potential contributor to endometriosis through microbial translocation, inflammation, and fibrosis. However, the consistency and clinical significance of this association remain uncertain. This systematic review evaluated the human and experimental evidence linking F. nucleatum with endometriosis and assessed the plausibility of a proposed oral microbe-host axis. Methods: PubMed/MEDLINE, Embase, Web of Science, and Google Scholar were searched from inception through August 31, 2026, following PRISMA 2020 guidelines. Human and animal studies reporting F. nucleatum or historically related F. nucleatum -complex taxa in relation to endometriosis were included. Risk of bias was assessed using a prespecified adapted ROBINS-I framework for human observational studies and SYRCLE for animal studies. Owing to substantial heterogeneity in anatomical compartments, detection methods, and outcomes, meta-analysis was not appropriate and findings were synthesized qualitatively. Results: Four human studies encompassing 384 participants at the study level were included, although analysis-specific denominators varied. Direct tissue evidence came from two studies and was conflicting: Muraoka et al. reported Fusobacterium positivity in 64.3% of endometrial samples from women with endometriosis versus 7.1% of controls in a 42-versus-42 tissue subset, whereas Graciano-España et al. found no significant case-control difference in F. nucleatum abundance among 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. All human studies were judged at serious overall risk of bias, and certainty of evidence was very low. Experimental evidence suggesting TGF-β-mediated lesion growth and fibrosis derived principally from one translational study and lacked independent replication. Conclusions: Current evidence supports biological plausibility but not a consistent or causal association between F. nucleatum and endometriosis. Direct tissue evidence is limited to two conflicting studies, while non-tissue microbiome findings are indirect. Standardized contamination-controlled sampling, paired anatomical-site sampling, strain-level analyses, and longitudinal studies are required before microbial translocation, temporality, causality, or antimicrobial treatment can be established. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261337885 .

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