Polycystic ovary syndrome (PCOS) is a complicated, endocrine-endemic disorder with a prevalence rate of 8-13% in reproductive-age women in the world, which manifests through insulin resistance, hyperandrogenism, and reproductive dysfunction. Despite its high global prevalence, existing therapeutic interventions focus predominantly on symptom management rather than targeting the heterogeneous and multifactorial pathophysiology of the syndrome. Intestinal barrier integrity is destroyed by dysbiosis of the gut microbiota and induces endotoxemia and chronic low-grade inflammation through signalling pathways, such as LPS-TLR4-NF-kB signalling, which contribute to increased insulin resistance and androgen excess. These mechanistic pathways we dissect include changes in short-chain fatty acids (SCFAs), bile acid metabolism, involvement of FXR and TGR5 receptors, neuroendocrine regulation of the gut-brain axis, and microbial metabolites (tryptophan and agmatine), which altogether alter metabolic and reproductive abnormalities in PCOS. The preclinical evidence in the area of fecal microbiota transplantation proves the causal component of microbiota imbalance in the phenotype of PCOS. Dietary interventions that have been reviewed are fiber and resistant starch modulation, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and pharmacotherapies like metformin, which also alter the microbiome. They are heading towards individualized microbiome-based therapies and diagnostics, aided by artificial intelligence and standardized biomarkers. This review explains the emerging role of the gut-insulin axis as an important factor in the pathogenesis of PCOS and uses a novel way of combining them as a radical intervention for personalized and innovative PCOS treatment, which has the potential to enhance metabolic and endocrine health, as well as reproductive outcomes.
