Metagenomic analysis identified microbiome alterations and pathological association between intestinal microbiota and polycystic ovary syndrome Original paper

What was studied?

This cross-sectional metagenomic sequencing study investigated gut microbiome signatures in polycystic ovary syndrome (PCOS) using shotgun sequencing to characterize species-level and functional microbial differences. The focus keyphrase PCOS gut microbiome signatures frames the study’s goal: linking specific microbial alterations with endocrine and metabolic features of PCOS. By employing metagenomic species (MGS) clustering and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation, the researchers evaluated how microbiome composition and microbial metabolic pathways correlate with hyperandrogenism, luteinizing hormone (LH) excess, antimüllerian hormone (AMH) elevation, and body mass index (BMI). This high-resolution sequencing approach surpassed traditional 16S methods, enabling strain-level differentiation and functional predictions relevant to pathological mechanisms such as inflammation, intestinal permeability change, and microbial metabolite–mediated endocrine disturbances.

Who was studied?

The analysis involved 28 Han Chinese women aged 20–35 years receiving care at a reproductive medicine center: 14 with PCOS fulfilling all Rotterdam criteria and 14 controls with regular cycles and tubal-factor infertility. Participants were stratified by BMI using Chinese-specific cutoffs and screened to eliminate confounding conditions such as thyroid disease, diabetes, recent antibiotic exposure, or hormone therapy. All provided stool samples and detailed diet questionnaires, ensuring that microbiome differences reflected disease-specific alterations rather than dietary or medication-related effects. Blood samples collected on cycle day 3 provided corresponding endocrine and metabolic data for correlation networks linking MGS profiles to reproductive hormones and glucose handling.

Most important findings

Metagenomic profiling revealed substantial species-level shifts distinguishing PCOS from controls. Women with PCOS exhibited increased abundance of Parabacteroides merdae, Bacteroides fragilis, Escherichia spp., Shigella spp., and multiple Enterobacteriaceae strains—microbes often associated with inflammation, mucin degradation, and metabolic disturbance. In contrast, controls showed enrichment of Faecalibacterium prausnitzii, Blautia hydrogenotrophica, and Bacteroides intestinalis, taxa known to produce butyrate and contribute to epithelial health. The correlation network highlighted strong positive intra-PCOS microbial clustering and negative correlations with control-enriched microbes, indicating distinct ecological community structures. MGS positively associated with PCOS—including Enterobacteriaceae, P. merdae, and B. fragilis—correlated with testosterone, LH, AMH, and higher BMI. Control-associated microbes correlated negatively with reproductive hormone levels, suggesting protective roles. KEGG functional analysis identified 389 PCOS-enriched orthologs pointing to disrupted mucin barriers, increased gut permeability, enhanced lipopolysaccharide (LPS) biosynthesis, elevated reactive oxygen species (ROS) tolerance, and microbial contributions to metabolic endotoxemia.

Key implications

The findings reinforce a mechanistic model in which dysbiosis amplifies PCOS pathophysiology by altering host–microbe signaling, impairing gut barrier integrity, increasing LPS translocation, and promoting inflammatory and metabolic cascades that influence ovarian function and androgen metabolism. Microbial shifts may alter steroid hormone inactivation pathways (e.g., CYP3A4 suppression) and elevate metabolites such as trimethylamine (TMA), linking PCOS dysbiosis to cardiometabolic risks. The study supports the clinical potential of microbiome-targeted therapies—such as probiotics, prebiotics, and dietary modulation—to restore microbial equilibrium and mitigate PCOS-associated endocrine and metabolic disturbances.

Citation

Chu W, Han Q, Xu J, et al. Metagenomic analysis identified microbiome alterations and pathological association between intestinal microbiota and polycystic ovary syndrome. Fertil Steril. 2020;113(6):1286-1298. doi:10.1016/j.fertnstert.2020.01.027