Abstract
Polycystic ovary syndrome (PCOS) is a prevalent chronic disorder characterized by reproductive, endocrine, and metabolic abnormalities in women worldwide. Increasing evidence has implicated the gut microbiota in the pathogenesis of PCOS, raising the possibility that probiotic interventions could offer therapeutic benefits. Akkermansia muciniphila (AKK), known for its metabolic and immunomodulatory properties, remains underexplored in the context of PCOS. In this study, we utilized a dehydroepiandrosterone (DHEA)-induced PCOS model in Sprague-Dawley (SD) rats to investigate the therapeutic potential of a novel AKK strain, PROBIO (referred to as AP). Treatment with AP significantly alleviated multiple PCOS-related phenotypes, including hyperandrogenism, elevated luteinizing hormone to follicle-stimulating hormone (LH/FSH) ratio, disrupted estrous cycle, abnormal ovarian morphology, and impaired glucose metabolism. Mechanistically, 16S rRNA gene sequencing and untargeted metabolomics revealed that AP partially exerted its beneficial effects by modulating DHEA-induced gut microbiota dysbiosis. Notably, metabolomic profiling indicated enhanced arginine biosynthesis and increased serum L-arginine levels in AP-treated rats. Consistently, in vivo supplementation with L-arginine reproduced the therapeutic effects of AP, ameliorating hyperandrogenism, LH/FSH imbalance, ovarian abnormalities, and estrous cycle irregularities in DHEA-induced PCOS rats. Taken together, these findings suggest that AP ameliorates PCOS phenotypes by restoring gut microbial composition, modulating host metabolism, and promoting L-arginine biosynthesis. This study highlights the potential of AP as a novel probiotic-based intervention for PCOS and underscores the therapeutic relevance of L-arginine in managing this disorder.