Changes in Metabolites and Microbial Communities in Follicular Fluid Associated With Ovarian Function in Patients With Polycystic Ovary Syndrome

ABSTRACT Polycystic ovary syndrome (PCOS) is a well‐documented endocrine disorder associated with metabolic abnormalities. Research has indicated potential links between PCOS and the gut microbiome, and the presence of microbial communities in follicular fluid (FF) has been demonstrated; however, their functional interplay with metabolites has not been elucidated. This case–control study involved 40 patients with PCOS and 40 controls matched for age. A comprehensive analysis of FF metabolites and microbial communities by means of metabolomics analysis and 16S rDNA sequencing was performed. Twelve metabolites and 15 microbial communities were significantly different between the PCOS and control groups. AMH and AFC were significantly associated with the majority of the differentially abundant metabolites and bacteria, suggesting a potential association between FF components and ovarian function. In this study, we found that D‐glucose and Alicyclobacillus were the most important variables in the metabolite model and microbial model, respectively. Mechanistically, Alicyclobacillus acidoterrestris , Terrimonas ferruginea , or Terrimonas pekingense can efficiently utilize glucose thereby reducing FF glucose levels, which provides insights into the microbiome–metabolite connection. These findings suggest a potential link among bacteria–metabolite–ovarian function, which could have implications for understanding the pathophysiology of PCOS and developing novel diagnostic and therapeutic strategies targeting metabolic and microbial aspects.