Gut microbiota plays a role in the development of polycystic ovary syndrome and its metabolic disorders

Abstract

Exploring the associations between PCOS metabolic disorders and its composition of gut microbiota. We compared the gut microbiota of 20 PCOS patients (lean PCOS individuals, PL, n = 10; overweight/obese PCOS individuals, PO, n = 10) with 20 healthy controls (lean control individuals, CL, n = 10; overweight/obese control individuals, CO, n = 10) by collecting their fecal samples. And we compared the metabolic markers between PCOS patients and the controls by collecting their blood samples, hoping to find out metabolites that connect gut microbiota with the development of PCOS and its metabolic disorders. 40 women in reproductive stage were recruited at the Sun Yat-Sen Memorial Hospital. Fecal samples were stored at -80°C within 20 minutes of collection for 16S rRNA Amplicon Sequencing. After an overnight fast, all participants underwent an oral glucose tolerance test. Blood was sampled frequently for measurement of blood glucose and plasma insulin, blood cholesterol, triglyceride, HDL-C and LDL-C. Plasma inflammatory factors such as hsCRP, LBP, TNF-α, IL-1, IL-6, IL-8 and basal hormone such as FSH, LH, PRL, estradiol and total testosterone were also detected. Statistical analyses were performed using IBM SPSS statistics 20.0 for clinical data, QIIME(v1.80) and Metastats for gut microbiota sequence data. Women with PCOS had higher levels of fasting insulin levels as well as higher homeostasis model assessment of insulin resistance (HOMA-IR) values and triglyceride level. Inflammatory biomarkers such as hsCRP, LBP, IL-6 and IL-8 all showed a higher trend in PCOS group, but the difference was not statistically significant. Metabolic disorders in PCOS were associated with reduced biodiversity in gut microbiota. Women with PCOS had less OTUs number compared to healthy women(190.60±63.12 VS 205.40±41.07), although the result was not statistically different. Besides, women with PCOS tended to have lower alpha and beta diversity in gut microbiota. Spearman correlation analysis showed that metabolic disorders were associated with changes in gut microbiota: 0h insulin, 2h insulin, and HOMA-IR values were negatively correlated with species richness (r=-0.369, -.0425, -0.356, p<0.05). The content of genus Desulfovibrio in patients with PCOS was positively correlated with 0h glucose, 0h insulin, HOMA-IR, LDL (r=0.485, 0.604, 0.640, 0.472, p<0.05). Genus Streptococcu was positively correlated with BMI, 1h blood glucose, 2h blood glucose, 2h insulin, HOMA-IR, cholesterol (r=0.492, 0.485, 0.548, 0.477, 0.458, 0.516, p<0.05). Our study demonstrated that women with PCOS had lower biodiversity in gut microbiota, of which were closely associated with insulin resistance and abnormal lipid metabolism. Our findings suggest that changes in the gut microbiome may influence the development and pathology of PCOS and its metabolic disorders as well.