<b>Gut Metabolic Signatures in Polycystic Ovary Syndrome: Insights from Fecal Untargeted Metabolomics</b>

<b>Background: </b>Polycystic Ovary Syndrome (PCOS) is a complex endocrine and metabolic disorder, increasingly associated with gut microbial dysbiosis. Fecal metabolomics offers a promising approach to explore gut microbial activity and its metabolic consequences, yet remains underexplored in PCOS research, particularly in diverse populations.<b>Objective: </b>To investigate fecal metabolic alterations in women with PCOS compared to healthy controls using an untargeted metabolomics approach.<b>Methods: </b>Fecal samples from 24 PCOS women and 30 age-matched healthy controls were subjected to untargeted metabolite profiling using liquid chromatography-mass spectrometry. Multivariate statistical analyses, including PCA and PLS-DA, were performed to identify significant discriminatory features. Differential metabolites were subjected to pathway enrichment analysis to explore their biological significance.<b>Results: </b>A clear metabolic distinction was observed between PCOS and control groups. In total, 115 metabolites were significantly altered, with 15 upregulated and 118 downregulated in PCOS women. Identified metabolites primarily belonged to classes including bile acids, amino acids, steroid hormones, fatty acids, and phenylpropanoids. Pathway enrichment analysis revealed significant alterations in steroid biosynthesis, bile acid metabolism, tryptophan metabolism, and amino acid biosynthesis. Notably, reduced levels of Glu-CDCA and cholic acid 3,7-diacetate suggested disruptions in bile acid transformation. Additionally, alterations in dehydroepiandrosterone (DHEA) derivatives and tryptophan-related metabolites indicated potential dysregulation of hormonal and neurotransmitter pathways.<b>Conclusion:</b> Fecal metabolomic profiling highlights distinct metabolic perturbations in women with PCOS, particularly involving bile acids, steroids, and amino acids. These findings provide insights into gut-associated metabolic disruptions in PCOS and suggest potential pathways for targeted therapeutic interventions.<b>Keywords:</b> Polycystic Ovary Syndrome, Fecal metabolome, Untargeted metabolomics, Bile acids metabolism, Steroids hormones, Gut microbiota.