The role of Fusobacterium nucleatum in the pathogenesis of endometriosis: A microbial and microenvironmental perspective

Endometriosis is a chronic, inflammatory gynecological condition characterized by the ectopic growth of endometrial-like tissue, with an unclear etiology and limited treatment efficacy. Recent studies implicate the oral and gut commensal bacterium Fusobacterium nucleatum in the pathogenesis of endometriosis, with uterine colonization reported in up to 64% of affected women. This review highlights the potential role of F. nucleatum in disease progression, particularly through its metabolic activation within the endometrial microenvironment. We explore the contribution of key bacterial metabolites (formate, lactate, and hydrogen sulfide), proteins (FadA and Fap2), and lipids (oxidized LDL, lysophosphatidylcholines, and saturated fatty acids) to inflammation, immune evasion, and epithelial-mesenchymal transition (EMT), features that overlap with tumor biology. The review also investigates the preferential triggers of F. nucleatum translocation into the endometrium. Host factors such as hypoxia, estrogen dominance, and retrograde menstruation appear to create a permissive microenvironment that potentially facilitates F. nucleatum colonization and virulence. While current therapeutic strategies largely neglect microbial involvement, emerging approaches including targeted antimicrobials, probiotics, immunomodulators, and microenvironmental modulation offer promising avenues for microbiome-informed endometriosis management. This narrative review also underscores the urgent need for longitudinal, in vivo studies to characterize the relationship between the oral, gut, and endometrial microbiomes and their impact on disease onset and progression.