Multi-Omic Profiling of Gut Microbiota and Fecal Metabolites in Patients With Polycystic Ovary Syndrome: A Cross-Sectional Study

<h4>Background and aim</h4>Intestinal flora composition in polycystic ovary syndrome (PCOS) varies, and the relationship between intestinal flora, fecal metabolites, clinical characteristics, and PCOS pathogenesis remains unclear. This study aimed to elucidate the gut microbiota characteristics of patients with PCOS, focusing on changes in normal-weight individuals, to provide new insights into its pathogenesis.<h4>Methods</h4>We combined 16S rRNA gene sequencing re-analysis with metagenomics and metabolomics to investigate gut microbiota and fecal metabolome alterations in PCOS. We re-analyzed our previous data on normal-weight women with PCOS (PCOS, <i>n</i> = 24; healthy controls [HC], <i>n</i> = 12) and the public databases (PCOS, <i>n</i> = 98; HC, <i>n</i> = 71) to further investigate the structure and function of the PCOS intestinal flora. Subsequently, from our previous study samples, we selected 10 patients residing in the Kaifu district, and their fecal samples (normal-weight PCOS group, <i>n</i> = 6; HC group, <i>n</i> = 4) were analyzed using metagenomic sequencing and non-targeted fecal metabolomics. Finally, the correlations among intestinal flora, fecal metabolites, and clinical indicators were evaluated.<h4>Results</h4>Based on the 16S rRNA data reanalysis, there were no significant differences in beta and alpha diversity between PCOS and normal controls. However, the PCOS group displayed a significantly higher relative abundance of Ruminococcus, Lachnospiraceae, and Escherichia-Shigella (<i>p</i> < 0.05) but a significantly lower relative abundance of Prevotella (<i>p</i> < 0.05) compared with the HC group. Subsequent metagenomics and metabolomics analyses revealed functional alterations, particularly in pathways related to secondary bile acid and lipid metabolism. Furthermore, Ruminococcus and Roseburia were positively correlated with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and negatively correlated with high-density lipoprotein (HDL) in patients with normal-weight PCOS.<h4>Conclusions</h4>This study highlights gut microbial dysbiosis as a key feature of PCOS. Reanalysis of 16S rRNA data revealed specific taxonomic shifts without altering overall diversity, notably an enrichment of <i>Ruminococcus</i> and a depletion of <i>Prevotella</i>. Furthermore, our metagenomics study identified functional reprogramming in pathways related to secondary bile acid and lipid metabolism. Crucially, even in normal-weight PCOS patients, these microbial alterations significantly correlated with adverse metabolic profiles (heightened insulin resistance and lower HDL levels), highlighting the microbiome as a potential therapeutic target.<h4>Ethical review no</h4>CHiECRT1900028223.