Gypenosides ameliorate polycystic ovary syndrome via gut microbiota modulation: An integrated gut microbiome and...

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder with complex metabolic and reproductive manifestations. Gut microbiota dysbiosis has emerged as a key factor in PCOS, yet the causal role of microbiota-targeted interventions remains to be fully defined. In a letrozole-induced rat model, we show that gypenosides (GPs)-bioactive saponins from Gynostemma pentaphyllum-alleviate weight gain, hormonal imbalance, and estrous cycle disruption, alongside reducing systemic oxidative stress and inflammation. Integrated ovarian transcriptomics and gut microbiome 16S rRNA sequencing reveal that GPs modulate ovarian gene expression related to inflammation and cellular function while reshaping gut microbiota by enriching beneficial genera including Lactobacillus and Romboutsia. Fecal microbiota transplantation (FMT) establishes causality: PCOS-derived microbiota transfers disease traits to normal recipients, whereas GPs-conditioned microbiota alleviates PCOS phenotypes in recipients. These findings demonstrate that GPs act through a "gut microbiota-oxidative stress-ovary" axis, supporting GPs as a promising microbiota-targeted intervention for PCOS management.