Decreased Diversity of the Gut Microbiome in Women with Polycystic Ovary Syndrome Is Correlated with Hyperandrogenism

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. In addition to anovulation and hyperandrogenism, a majority of women with PCOS have metabolic abnormalities that result in an increased risk of type 2 diabetes and cardiovascular disease. Although androgen excess is considered to be a cornerstone in the pathology of PCOS, the etiology of this disorder remains elusive. Studies have demonstrated that changes in the intestinal (gut) microbiome are associated with metabolic disorders such as obesity and type 2 diabetes, and that the gut microbiome may play a causal role in these disorders. Recent studies in Caucasian and Han Chinese women reported a significant decrease in gut bacterial alpha diversity (species richness) in women with PCOS compared with healthy women and we also observed a decrease in gut alpha diversity in a hyperandrogenic, letrozole-induced PCOS mouse model compared with placebo controls. Here, we investigated whether changes in alpha diversity in women with PCOS correlated with specific endocrine parameters. We also asked whether there was a significant change in the diversity of the gut microbiome in women with polycystic ovarian morphology (PCOM) that lack the other diagnostic criteria of PCOS. Rectal swabs and clinical data were collected from Caucasian patients recruited from the Infertility Clinic at Poznan University of Medical Sciences. Gut microbial diversity profiles of healthy women (n=47), women with PCOM (n=42), and women diagnosed with PCOS using the Rotterdam criteria (n=69) were determined by next-generation sequencing of bacterial 16S ribosomal RNA genes and bioinformatics analysis using the QIIME pipeline. Our results showed that women with PCOS had a significant decrease in overall species richness and phylogenetic diversity compared with healthy women. Women with PCOM also had a change in gut microbial diversity that was intermediate between that of healthy women and women with PCOS. Multiple regression analysis of diagnostic and physiological parameters showed that hyperandrogenism had the highest correlation with alpha diversity. Additional single factor linear regression analyses found a significant negative correlation between alpha diversity and both total testosterone levels and hirsuitism, while no correlations were observed with age or BMI. Altogether, these results suggest that hyperandrogenism may play a critical role in altering the gut microbiome in women with PCOS.