Profile of Bile Acid Metabolomics in the Follicular Fluid of PCOS Patients Original paper

What was studied?

This study examined the profile of bile acid metabolomics in the follicular fluid (FF) of women with polycystic ovary syndrome (PCOS). For the first time, researchers evaluated how the composition of bile acids in the ovarian micro-environment differs between PCOS and non-PCOS women, aiming to elucidate the potential roles of bile acids in follicular development and ovulatory dysfunction. Using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS), the study quantified 24 bile acid metabolites and assessed their clinical correlations in relation to hormone levels and ovarian characteristics.

Who was studied?

The study included 35 women diagnosed with PCOS based on the Rotterdam criteria and 31 control women undergoing assisted reproduction for male or tubal factor infertility, all with normal menstrual cycles and ovarian function. All participants were under 40 years old and had no history of endocrine disorders, ovarian surgery, or liver dysfunction. The researchers ensured matched baseline characteristics, such as liver enzyme levels and BMI, to avoid confounding bile acid data with liver metabolism variations. Follicular fluid was collected during oocyte retrieval procedures as part of IVF or ICSI cycles.

What were the most important findings?

The study identified a distinct alteration in bile acid composition in the follicular fluid of PCOS patients. Although the total bile acid concentration was not significantly different, specific metabolites showed statistically significant elevations. Four bile acid metabolites, glycocholic acid (GCA), taurocholic acid (TCA), glycochenodeoxycholic acid (GCDCA), and chenodeoxycholic acid-3-β-D-glucuronide (CDCA-3Gln), were significantly higher in PCOS FF compared to controls. The increase was most notable in conjugated and primary bile acids, while levels of secondary and unconjugated bile acids remained unchanged.

GCDCA demonstrated a positive correlation with serum FSH and LH, suggesting its potential involvement in disrupted folliculogenesis and ovulation associated with PCOS. Similarly, CDCA-3Gln correlated with antral follicle count (AFC), indicating a possible relationship with ovarian reserve status. Importantly, there was no association between these bile acid changes and insulin sensitivity, highlighting a potential ovary-specific bile acid dysregulation in PCOS independent of systemic insulin resistance. These bile acids, particularly the conjugated primary forms, may reflect altered bile acid metabolism influenced by gut microbiota, especially given prior reports linking intestinal flora with circulating bile acid changes in PCOS. Although not directly assessed in this study, the elevated GCA and TCA levels echo findings from serum metabolomics that suggest microbial contributions, possibly involving Bacteroides and Clostridium species known to interact with bile acid pools.

What are the greatest implications of this study?

This study underscores the potential role of bile acid metabolites as contributors to the pathophysiology of PCOS, particularly within the ovarian micro-environment. It suggests that bile acid dysregulation may impact granulosa cell function and follicular development, which could influence ovulation. Identifying FF bile acids as potential biomarkers opens new diagnostic and therapeutic avenues, particularly in targeting the bile acid signaling axis or modulating gut microbiota to restore metabolic balance within the ovary. The findings encourage a shift toward integrating ovarian metabolomics with systemic and microbiome data to better characterize PCOS subtypes and treatment targets.