Microbiome in PCOS and Related Metabolic Traits

Despite gut microbiome being widely studied in metabolic diseases, its role in polycystic ovary syndrome (PCOS) has been scarcely investigated.The aim of our study was to test whether gut microbiome is associated with PCOS in late fertile age women including age- and BMI-matched controls. We also aimed to assess different metabolic and hormonal markers related to PCOS and their associations with the gut microbiome. The study population consisted of a subset of females in the longitudinal Northern Finland Birth Cohort 1966 (NFBC1966) which includes all expected births in 1966 in the two northernmost provinces of Finland. The NFBC1966 is a unique population-based cohort, which was established as a longitudinal research program to promote health and well-being of the population. At age 46 the women were invited for a follow-up and to fill in a questionnaire. During the latter follow-up, clinical examinations with blood and fecal sample collection, oral glucose tolerance test (OGTT) and anthropometric measurements were performed. A total of 311 women (103 PCOS and 207 age- and BMI-matched healthy controls) of which 303 women were included for analysis (102 PCOS and 201 age- and BMI-matched healthy controls).We first characterized the phylogenetic variation across all the samples (n = 303) at different taxonomic levels. Next, we assessed differences in the gut microbiome diversity (alpha and beta diversities) between controls and PCOS samples. We then investigated whether bacterial richness (Shannon index, as alpha diversity) and beta diversity were associated with clinical, hormonal and metabolic parameters for all women.Bacterial diversity indices did not differ significantly between PCOS and controls (Shannon diversity p = 0.979, unweighted UniFrac p = 0.175). Four genera whose balance helps to differentiate between PCOS and non-PCOS were identified. In the whole cohort, the abundance of two genera from Clostridiales, Ruminococcaceae UCG-002 and Clostridiales Family XIII AD3011 group, were correlated with several PCOS-related markers. Prediabetic PCOS women had significantly lower alpha diversity (Shannon diversity p = 0.018) and markedly increased abundance of genus Dorea (FDR = 0.03) compared to women with normal glucose tolerance. PCOS and non-PCOS women at late fertile age with similar BMI do not significantly differ in their gut microbial profiles. However, there are significant microbial changes in PCOS individuals depending on their metabolic health.