The gut–ovary axis in polyendocrine metabolic ovarian syndrome: Mechanisms, microbiome dysbiosis, and emerging therapeutic strategies

Abstract

Polycystic ovary syndrome (PCOS), recently termed polyendocrine metabolic ovarian syndrome (PMOS), is a heterogeneous endocrine–metabolic disorder characterized by reproductive, metabolic, and hormonal disturbances. Increasing evidence suggests that interactions between the gut microbiota and host physiology may be relevant to PMOS through pathways involving intestinal barrier function, inflammation, insulin sensitivity, steroid hormone metabolism, bile acid signaling, and gut–brain–ovary communication. This narrative review synthesizes current human and preclinical evidence on the gut–ovary axis in PMOS, with particular emphasis on microbial dysbiosis, proposed mechanistic pathways, microbiome‐related metabolic and endocrine interactions, and emerging therapeutic approaches. Human studies generally report associations between altered microbial composition and metabolic or reproductive features of PMOS, although findings vary considerably according to population characteristics, bodyweight, diagnostic criteria, sequencing methods, and analytical approaches. Experimental studies provide additional support for potential roles of microbial metabolites, intestinal permeability, immune signaling, and metabolic pathways, but these mechanisms have not been established as causal in humans. Microbiome‐targeted interventions, including probiotics, prebiotics, synbiotics, and dietary approaches, show potential, whereas fecal microbiota transplantation remains largely experimental. Conventional metabolic therapies, including glucagon‐like peptide‐1 receptor agonists, should be considered separately from microbiome‐targeted approaches. Overall, the gut–ovary axis represents a promising framework for understanding the systemic features of PMOS, but substantial heterogeneity, limited longitudinal human evidence, and underrepresentation of diverse populations currently limit translation into clinical practice.