Farah Elhennawy, Basmalah Naji, Alexandra E Butler
Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders worldwide, affecting 6-13% of reproductive-aged women and exerting a profound metabolic, reproductive and psychological toll. Emerging evidence suggests that the gut microbiome may be a potentially critical, yet under-recognized, contributor to the pathophysiology of PCOS. Alterations in microbial composition and function appear to influence hormonal imbalance, metabolic dysfunction and inflammatory processes that characterize the condition. However, much of the current evidence remains associative or derived from preclinical models, and the causal nature of these relationships is only beginning to be established through approaches such as Mendelian randomization. This literature review examines the evolving relationship between the gut microbiome and PCOS through a mechanism-guided, evidence-stratified framework, with particular focus on how microbiota-targeted interventions - including prebiotics, probiotics, synbiotics, dietary modifications and fecal microbiota transplantation, may modulate gut health and mitigate symptom severity. Across the reviewed studies, microbiome-targeted supplementation was associated with improvements in insulin sensitivity, reductions in systemic inflammation and favorable hormonal changes, although the strength of evidence varies across outcomes and intervention types. Importantly, PCOS heterogeneity, including differences in body mass index (BMI), insulin resistance status and phenotype, may influence both gut microbiota composition and therapeutic response, underscoring the need for phenotype-stratified research. These findings suggest that targeting the gut microbiome may serve as a promising adjunct to conventional PCOS management. Though further rigorous, long-term clinical trials are needed to advance both understanding and clinical translation.