Royal jelly enhances ovarian function by modulating taurocholic acid metabolism and attenuating oxidative stress in D-galactose-induced POI mice.

Premature ovarian insufficiency (POI) is a complex endocrine and metabolic disorder frequently associated with oxidative stress. Royal jelly (RJ) is a well-recognized natural functional food with multiple health benefits; however, its potential effects on POI remain unexplored. This study aimed to investigate the therapeutic potential and underlying mechanisms of RJ in a D-galactose (D-gal)-induced POI mouse model. The results showed that RJ increased serum estradiol (E2) levels, enhanced ovarian reserve and oocyte maturation, reduced ovarian oxidative stress, and ultimately improved the fertility of D-gal-treated mice. Integrated metagenomic and metabolomic analyses revealed that RJ alleviated D-gal-induced gut microbiota dysbiosis, notably increasing the abundance of Muribaculaceae bacterium, and restored levels of taurocholic acid (TCA), which positively correlated with both Muribaculaceae bacterium abundance and serum E2 levels. Importantly, TCA supplementation alone recapitulated the protective effects of RJ by reversing D-gal-induced reductions in E2 and anti-Müllerian hormone (AMH) levels, restoring follicle numbers, and alleviating oxidative stress. Mechanistically, TCA activated the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant pathway in ovarian tissue, while simultaneously enhancing intestinal β-glucuronidase activity to modulate systemic E2 metabolism. In conclusion, RJ alleviates D-gal-induced POI in mice by modulating the gut microbiota-bile acid-ovarian axis, providing novel insights into its potential application for POI prevention and treatment.