The role of gut microbiota mediated ferroptosis in PCOS and the therapeutic potential of Chinese herbal medicine

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine metabolic disorder whose pathogenesis remains incompletely understood. In recent years, the role of ferroptosis–a novel form of iron-dependent programmed cell death–in the pathogenesis of PCOS has gradually drawn attention. This review proposes an innovative perspective: gut microbiota dysbiosis may be a potential upstream trigger of ferroptosis in PCOS ovarian granulosa cells. Microbiome dysbiosis disrupts iron homeostasis and reduces the production of antioxidant metabolites such as short-chain fatty acids (SCFAs) and bile acids (BAs), thereby exacerbating systemic and local ovarian oxidative stress. This induces ferroptosis, leading to impaired follicular development and insulin resistance. Traditional Chinese Medicine (TCM) demonstrates significant potential in regulating gut microbiota and inhibiting ferroptosis. Based on this, this study explores the role of the gut microbiota-ferroptosis axis in PCOS, focusing on the scientific rationale and application prospects of treating PCOS by intervening in this axis using TCM monomers and compounds such as berberine and quercetin. With its multi-target regulatory effects and favorable safety profile, TCM may offer benefits as an adjunct or alternative to conventional therapies. This research aims to provide theoretical references for developing novel therapeutic strategies.