The gut-ovary axis: how microbial players orchestrate female reproductive health

Abstract

Ovarian dysfunction—encompassing polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), and ovarian aging—poses a significant challenge in reproductive medicine, largely due to the limited availability of etiology-based treatments. Emerging evidence positions the gut microbiota as a “virtual endocrine organ” that communicates with the ovary via a bidirectional gut-ovary axis. This axis operates through three primary mechanisms: microbial metabolite signaling, immune regulation, and hormonal crosstalk. In this review, we synthesize current evidence to delineate the potential associations between gut dysbiosis and ovarian pathology and evaluate the therapeutic potential of microbiota-targeted interventions, including fecal microbiota transplantation (FMT), probiotics, and dietary strategies. We further identify critical research gaps in causal validation and clinical translation, offering a perspective on future directions for the exploration of ovarian health management strategies based on modulation of the gut-ovary axis.