Gut microbiota dysbiosis in endometriosis: mechanistic insights and gut microbiota-targeted therapeutic strategies

Endometriosis (EMs) is a prevalent, estrogen-dependent gynecological disorder characterized by the ectopic implantation and proliferation of endometrial-like tissue outside the uterine cavity, affecting approximately 10% of reproductive-aged women globally. Despite its high incidence, the exact pathogenesis of EMs remains incompletely elucidated, and current clinical treatments are often limited by suboptimal efficacy and adverse effects. Accumulating evidence over the past decade has revealed a strong observational association between gut microbiota dysbiosis and EMs development, suggesting that the gut microbiota may serve as a novel potential target for understanding and managing this disease. This review systematically summarizes the potential mechanistic links underlying the interplay between gut microbiota dysbiosis and EMs progression, focusing on three core pathways: intestinal barrier dysfunction and microbial translocation, immune dysregulation and ectopic lesion immune escape, and estrogen metabolism disorder mediated by microbial enzymes and metabolites. In addition, this review stratifies gut microbiome profiles by EMs clinical subtypes (peritoneal, ovarian, deep infiltrating), clarifies anatomical correlations of the gut-lesion axis, and discusses confounding factors and causal inference methodologies. Beyond mechanistic insights, this review also discusses emerging gut microbiota-targeted therapeutic strategies for EMs, including probiotic supplementation, prebiotic intervention, fecal microbiota transplantation (FMT), and dietary modulation, with supplementary ethical considerations for FMT. Collectively, this review provides a comprehensive overview of the gut microbiota-EMs axis, highlighting current evidence levels and offering perspectives for the development of innovative, effective, and safe therapeutic approaches for EMs patients.