L-arginine alleviates polycystic ovary syndrome restore ovulation and androgen levels by regulating gut microbiota

Abstract Emerging research highlights the crucial role of gut microbiota and its metabolites in managing metabolic disorders, implicating their contribution to the pathophysiology of polycystic ovary syndrome (PCOS). The present study employed a multi-omics research approach encompassing metagenomics, metabolomics, and transcriptomics to investigate the etiology of PCOS. We focused our subsequent investigation on L-arginine (L-arg), as it is a metabolite significantly associated with alterations in the gut microbiome and PCOS clinical indicators. Using mouse models of antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT), we found that oral administration of L-arg reduced PCOS-like symptoms potentially through a mechanism of regulating the gut microbiome. In addition, a cohort of PCOS patients was established to evaluate the clinical effect of L-arg intervention. The results indicate that L-arg effectively improves menstrual regularity, total testosterone, free testosterone, free androgen index (FAI), uric acid (UA), and sex hormone-binding globulin (SHBG) levels. Collectively, these findings have expanded our understanding of the pathological mechanism of PCOS and suggest that L-arg may be an effective treatment for PCOS.