Circulating bile acid profile characteristics in PCOS patients and the role of bile acids in predicting the pathogenesis of PCOS Original paper

What was studied?

This original research investigated the alterations in circulating bile acid (BA) profiles in women with polycystic ovary syndrome (PCOS) and evaluated the potential of specific bile acid metabolites as biomarkers for predicting PCOS pathogenesis. The study analyzed serum samples from 408 women diagnosed with PCOS and 204 healthy controls matched for age and BMI. The team quantified 15 bile acid fractions using liquid chromatography–tandem mass spectrometry (LC-MS/MS), aiming to discern significant differences in bile acid composition between the two groups. The researchers further assessed the correlation of these bile acids with metabolic parameters, especially glucose metabolism and hyperandrogenism, and examined their diagnostic potential using multivariate statistical models such as OPLS-DA and XGBoost.

Who was studied?

The study included 408 women with PCOS diagnosed according to the Rotterdam 2003 criteria and 204 age- and BMI-matched non-PCOS controls. All participants were between 18–45 years old, with exclusions applied for conditions or medications that could affect bile acid metabolism or mimic PCOS symptoms. Comprehensive clinical, hormonal, metabolic, and imaging assessments were conducted to ensure accurate phenotyping. Importantly, the PCOS cohort was further divided into subgroups based on glucose tolerance (normal vs. impaired) and androgen status (hyperandrogenic vs. non-hyperandrogenic) to explore how bile acid profiles vary across PCOS phenotypes.

What were the most important findings?

The study identified significant alterations in circulating bile acid profiles in women with PCOS, particularly elevated levels of primary (CDCA) and secondary (LCA, DCA) unconjugated bile acids. Among 15 measured metabolites, five, including CDCA and LCA, were significantly different in PCOS patients and showed diagnostic potential. CDCA emerged as the most discriminatory metabolite. Notably, DCA correlated with insulin secretion markers such as fasting and postprandial insulin, though this relationship weakened after adjusting for testosterone, suggesting androgen modulation of these effects. Combined analysis of CDCA, LCA, and testosterone improved PCOS prediction over testosterone alone. These findings highlight a possible interaction between bile acid metabolism, gut microbiota (especially with DCA), and androgen excess in PCOS pathophysiology.

What are the greatest implications of this study?

This study underscores the potential of specific bile acids, particularly CDCA and LCA, as novel biomarkers for PCOS diagnosis and stratification, especially when used in combination with serum testosterone. It reveals that PCOS pathogenesis involves distinct alterations in bile acid metabolism, possibly through activation of alternative synthesis pathways and interaction with gut microbiota. The research contributes to a growing body of evidence supporting the integration of metabolic and microbial markers into PCOS diagnostics. Clinically, the findings advocate for more nuanced, biochemically informed approaches to PCOS diagnosis beyond current criteria, which do not capture metabolic and microbial heterogeneity. Future research should validate these biomarkers longitudinally and explore therapeutic interventions targeting bile acid pathways or microbiome modulation.