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

## TL;DR

This study finds that changes in follicular fluid metabolites and microbes are linked to ovarian function in PCOS patients, suggesting a new pathway for understanding and treating the condition.

## Contribution

The study reveals a functional connection between follicular fluid metabolites, microbial communities, and ovarian function in PCOS.

## Key findings

- D-glucose and Alicyclobacillus were the most significant variables in metabolite and microbial models, respectively.
- Alicyclobacillus acidoterrestris and Terrimonas species can utilize glucose, affecting follicular fluid glucose levels.
- AMH and AFC were significantly associated with differentially abundant metabolites and bacteria, indicating a link to ovarian function.

## 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.

Based on the integrated analysis of follicular fluid metabolites and microbial communities in patients with PCOS, this study reveals significant dysregulation in the follicular microenvironment. Key metabolites including D‐glucose and 25‐hydroxycholesterol show marked alterations, while microbial communities such as Alicyclobacillus and Terrimonas demonstrate distinctive abundance patterns. Importantly, specific bacteria like Alicyclobacillus acidoterrestris and Terrimonas species exhibit glucose‐utilizing capabilities that directly impact follicular fluid glucose levels. These findings establish a functional bacteria–metabolite–ovarian axis, where microbial metabolic activities interact with host metabolites to influence ovarian function, providing new insights into PCOS pathophysiology and potential therapeutic targets.