<i>Bifidobacterium animalis</i> BGI‐L99 Ameliorates Polycystic Ovary Syndrome by Modulating the Gut Microbiota‐Bile Acid‐IL‐22 Axis

ABSTRACT Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder tightly linked to gut microbiota dysbiosis. While probiotics present a promising therapeutic avenue, the underlying mechanisms remain largely unclear. Here, we investigated the efficacy and mechanism of Bifidobacterium animalis subsp. lactis BGI‐L99 in a dehydroepiandrosterone (DHEA)‐induced PCOS mouse. We found that oral administration of BGI‐L99 significantly ameliorated PCOS phenotypes, including restoring estrous cycle regularity, ameliorating depression‐like behaviors, reducing cystic follicles, decreasing serum testosterone, and increasing estradiol levels. Mechanistically, BGI‐L99 reshaped the gut microbiota and robustly increased the concentrations of beneficial bile acids, notably chenodeoxycholic acid (CDCA) and tauroursodeoxycholic acid (TUDCA). This metabolic shift was associated with a significant upregulation of the protective cytokine interleukin‐22 (IL‐22) in both serum and tissues. Crucially, direct supplementation with CDCA or TUDCA could mimic the beneficial effects of probiotics, effectively restoring the estrous cycle, reducing polycystic follicles, increasing corpus luteum count, and normalizing serum T and E2 levels. These findings confirm the pivotal role of these bile acids in alleviating PCOS symptoms and elevating IL‐22 levels. Our findings demonstrate that B. animalis BGI‐L99 exerts its alleviative effects on PCOS by modulating the gut microbiota‐bile acid‐IL‐22 axis, identifying this pathway as a promising target for probiotic‐based interventions.