Gut Microbiome Dysbiosis in Polycystic Ovary Syndrome, Endometriosis, and Ovarian Disorders: Mechanistic Insights and Therapeutic Implications

Abstract

Gut microbiome dysbiosis has emerged as a mechanistically coherent contributor to polycystic ovary syndrome (PCOS), endometriosis, premature ovarian insufficiency (POI), epithelial ovarian cancer (EOC), and diminished ovarian reserve (DOR). Across clinical cohorts, a convergent microbial signature recurs: depletion of butyrate-producing commensals, expansion of Gram-negative inflammatory taxa, compromised intestinal barrier integrity, and elevated circulating lipopolysaccharide (LPS) — a state termed metabolic endotoxaemia. From this shared microbial foundation, condition-specific pathological pathways diverge. In PCOS, bidirectional androgen–microbiome cycles sustain hyperandrogenaemia and insulin resistance through β-glucuronidase-mediated hormone reactivation and short-chain fatty acid (SCFA) depletion. In endometriosis, oestrobolome dysregulation amplifies systemic oestrogen recirculation while LPS-driven peritoneal immune polarisation facilitates ectopic lesion survival. In EOC, SCFA depletion attenuates anti-proliferative histone deacetylase (HDAC) inhibition, and gut microbiome composition modulates response to immune checkpoint inhibitors. Emerging therapeutic approaches — including synbiotic supplementation, Mediterranean dietary modification, faecal microbiota transplantation (FMT), and microbiome-modulating pharmacological agents such as metformin — show mechanistically coherent but clinically modest effects, with reproductive endpoint data from randomised controlled trials (RCTs) largely absent. This review critically synthesises mechanistic and clinical evidence linking gut dysbiosis to ovarian disorders, evaluates the central pathophysiological pathways, and appraises the therapeutic landscape. Methodological standardisation, longitudinal causal study designs, and adequately powered RCTs with reproductive and oncological endpoints are identified as priority needs. Gut dysbiosis is not the sole determinant of these complex conditions, but represents a modifiable contributor of growing clinical relevance.