Gut microbiota in diabetic-linked polycystic ovarian syndrome: Mechanisms and therapeutic insights

Polycystic ovarian syndrome (PCOS) is a complex multisystem disorder prevalent among women of reproductive age, commonly marked by insulin resistance, hyperinsulinemia, and metabolic disruptions such as hypertension and dyslipidemia, which elevate risks of cardiovascular disease and hepatic steatosis. Recent advances underscore the gut microbiome's critical role in modulating insulin resistance and metabolic homeostasis in PCOS. This review highlights novel insights into gut dysbiosis-driven inflammation, gut-brain hormonal signaling, and immune modulation as underlying mechanisms connecting PCOS with metabolic dysfunction and diabetes. We comprehensively analyzed studies up to September 2024 on gut microbiota, diabetes, PCOS, and metformin, exploring emerging perspectives on the microbiome's therapeutic potential in managing PCOS. Metformin's dual role in insulin sensitivity improvement and gut microbiome modulation is emphasized, including its indirect effects on weight management. This review also identifies gaps in current research, urging a shift toward precision therapies targeting microbiome-related pathways in PCOS. Further exploration of the gut-brain axis, pathogen-associated molecular patterns, and the need for controlled clinical trials are discussed to enhance therapeutic approaches.