Structural and functional profiles of the gut microbial community in polycystic ovary syndrome with insulin resistance (IR-PCOS): a pilot study Original paper

What was studied?

This study investigated the IR-PCOS gut microbiome, comparing intestinal microbial structure and predicted metabolic functions in women with insulin-resistant polycystic ovary syndrome (IR-PCOS), non-insulin-resistant PCOS (NIR-PCOS), and healthy controls. Using 16S rRNA sequencing of stool samples, the researchers sought to determine whether insulin resistance is linked to distinct microbial signatures beyond those attributable to PCOS alone. The analysis included microbial diversity measures, taxonomic shifts at phylum-to-genus levels, and microbiome–clinical parameter correlations. Functional predictions using PICRUSt were used to infer potential metabolic consequences of these compositional shifts, emphasizing pathways relevant to steroidogenesis, inflammation, and carbohydrate, amino acid, and lipid metabolism.

Who was studied?

Twenty-nine premenopausal women were initially recruited, and after exclusions for obesity, smoking, antibiotic use, and abnormal glucose response, 25 participants remained: eight healthy controls, eight NIR-PCOS patients, and nine IR-PCOS patients. All participants were within a similar age and BMI range, reducing confounding by adiposity. Dietary patterns were also balanced across groups. PCOS diagnoses followed Rotterdam criteria, and insulin resistance was defined via HOMA-IR thresholds and oral glucose tolerance testing. This carefully selected cohort enabled assessment of microbiome differences attributable specifically to PCOS phenotypes and insulin resistance.

Most important findings

The IR-PCOS gut microbiome exhibited the greatest dysbiosis. Alpha diversity (observed OTUs and Shannon index) was lowest in IR-PCOS patients, and beta-diversity plots showed clear separation between IR-PCOS and healthy controls. Across samples, Bacteroidetes and Firmicutes dominated, but their balance shifted significantly: NIR-PCOS women showed increased Firmicutes: Bacteroidetes ratios, whereas IR-PCOS patients had the opposite trend. A pronounced and clinically relevant pattern emerged at the family level. Bacteroidaceae abundance increased progressively from healthy controls to NIR-PCOS to IR-PCOS, while Prevotellaceae were sharply reduced, nearly absent in most PCOS participants. Additional reductions in Ruminococcaceae and Lachnospiraceae were observed in IR-PCOS, taxa typically associated with butyrate production and mucosal health. Correlation analyses showed Bacteroidaceae were positively associated with insulin resistance, testosterone, lipids, and inflammatory cytokines, while Prevotellaceae demonstrated inverse correlations and a positive association with estradiol. Functional predictions illustrated 73 altered metabolic pathways in PCOS patients, with IR-PCOS showing distinct enrichment in lipopolysaccharide biosynthesis and steroid hormone biosynthesis—mechanisms likely contributing to androgen excess and chronic inflammation.

Key implications

The findings suggest that insulin resistance in PCOS is associated with a more severe gut microbiome disturbance than PCOS alone. Elevated Bacteroidaceae and depleted Prevotellaceae may contribute to metabolic dysfunction by promoting low-grade inflammation, impairing gut barrier integrity, and influencing hormone regulation. The distinct microbial and functional patterns in IR-PCOS indicate that microbiome-targeted interventions may need to differentiate between PCOS phenotypes. These results support the potential for precision microbiome therapeutics, including restoration of SCFA-producing taxa, reduction of pro-inflammatory bacteria, and modulation of microbial metabolic pathways relevant to steroidogenesis.

Citation

Zeng B, Lai Z, Sun L, et al. Structural and functional profiles of the gut microbial community in polycystic ovary syndrome with insulin resistance (IR-PCOS): a pilot study. Research in Microbiology. 2019;170(1):43-52. doi:10.1016/j.resmic.2018.09.002