High-altitude Lactiplantibacillus plantarum AL4510 alleviates superovulation-induced premature ovarian failure via the gut-ovary axis

Premature ovarian failure (POF) is characterized by early loss of ovarian function and is closely associated with oxidative stress, inflammation, and endocrine dysregulation. This study investigated whether Lactiplantibacillus plantarum AL4510, a high-altitude probiotic isolated from the Qinghai-Xizang Plateau, could alleviate POF through the gut-ovary axis. Whole-genome sequencing revealed that AL4510 possesses a strong antioxidant genetic repertoire, particularly genes involved in glutathione metabolism. A consecutive superovulation-induced POF mouse model was established and treated with oral AL4510. Ovarian function, gut microbiota, microbial metabolites, and ovarian transcriptomic profiles were comprehensively evaluated. AL4510 restored ovarian reserve and endocrine balance, reduced follicular atresia, oxidative stress, inflammation, and cellular senescence, and improved intestinal barrier integrity. It also reshaped the gut microbiota by enriching beneficial short-chain fatty acid (SCFA)-producing bacteria and restoring SCFA production. Multi-omics analyses revealed recovery of steroid hormone biosynthesis, glutathione metabolism, and inflammation-related pathways, while correlation analyses demonstrated coordinated interactions among gut microbes, metabolites, and reproductive hormones. Collectively, these findings demonstrate that L. plantarum AL4510 alleviates POF through microbiota-mediated metabolic and antioxidant regulation, highlighting the potential of high-altitude probiotics as a dietary strategy for improving ovarian health.