A New Perspective on Endometriosis: How Gut and Reproductive Tract Microbiota Influence Disease Progression?

IMPORTANCE: Endometriosis, a chronic inflammatory condition affecting 10% of reproductive-aged individuals, remains underdiagnosed and poorly managed due to a limited understanding of its pathogenesis. Emerging evidence highlights the gut and reproductive tract microbiota as key modulators of estrogen metabolism, immune dysregulation, and inflammation, offering novel insights into disease mechanisms and therapeutic opportunities. OBJECTIVE: To synthesize current evidence on the mechanistic roles of microbiota in endometriosis pathogenesis, evaluate the diagnostic and therapeutic potential of microbial biomarkers and microbiota-targeted interventions, and identify priorities for translational research. EVIDENCE ACQUISITION: A systematic review of PubMed, Scopus, and Web of Science databases identified preclinical and clinical studies exploring microbiota-endometriosis interactions. The search strategy incorporated the terms "endometriosis" in combination with "microbiota," "reproductive tract," and "gut" to investigate microbial associations within gastrointestinal and reproductive systems in the context of the disease. RESULTS: Dysbiotic microbial profiles, characterized by reduced Lactobacillus and elevated Fannyhessea species, correlate with altered estrogen metabolism, pro-inflammatory cytokine production (eg, IL-6, TNF-α), and impaired immune surveillance in endometriosis. Preclinical studies demonstrate that probiotics and FMT attenuate lesion growth and inflammation in animal models, though human data remain limited. Noninvasive microbial signatures show promise for diagnostic applications, while causal validation in germ-free models and personalized microbiota-based therapies represent critical research gaps. CONCLUSIONS: The microbiota modulates endometriosis progression through hormonal, immune, and inflammatory pathways. Microbial biomarkers and therapies may improve diagnosis and treatment but require rigorous clinical validation. RELEVANCE: Advancing microbiota research could enable noninvasive diagnostics, precision therapies, and prevention strategies.