Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study

Abstract

BackgroundPolycystic ovary syndrome (PCOS) is a common female endocrinopathy of unclear origin characterized by hyperandrogenism, oligo-/anovulation, and ovarian cysts. Women with PCOS frequently display overweight, insulin resistance, and systemic low-grade inflammation. We hypothesized that endotoxemia resulting from a leaky gut is associated with inflammation, insulin resistance, fat accumulation, and hyperandrogenemia in PCOS. In this pilot study, we compared the stool microbiome, gut permeability, and inflammatory status of women with PCOS and healthy controls.Methods16S rRNA gene amplicon sequencing was performed on stool samples from 24 PCOS patients and 19 healthy controls. Data processing and microbiome analysis were conducted in mothur and QIIME using different relative abundance cut-offs. Gut barrier integrity, endotoxemia, and inflammatory status were evaluated using serum and stool markers and associations with reproductive, metabolic, and anthropometric parameters were investigated.ResultsThe stool microbiome of PCOS patients showed a lower diversity and an altered phylogenetic composition compared to controls. We did not observe significant differences in any taxa with a relative abundance>1%. When looking at rare taxa, the relative abundance of bacteria from the phylum Tenericutes, the order ML615J-28 (phylum Tenericutes) and the family S24-7 (phylum Bacteroidetes) was significantly lower and associated with reproductive parameters in PCOS patients. Patients showed alterations in some, but not all markers of gut barrier function and endotoxemia.ConclusionPatients with PCOS have a lower diversity and an altered phylogenetic profile in their stool microbiome, which is associated with clinical parameters. Gut barrier dysfunction and endotoxemia were not driving factors in this patient cohort, but may contribute to the clinical phenotype in certain PCOS patients.

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

“…Recent studies have found that the profiles of bacterial abundance exhibit similarities between the orders Clostridales and Bacteroidales . 22 , 31 , 32 Obese and non-obese women with PCOS had enriched Bacteroidetes and a decreased abundance of Akkermansia (of the phylum Verrucomicrobia ), Alistipes, Corprococcus , and Ruminococcus . 33 Akkermansia prevalence decreased in diet-induced obesity rats and was inversely correlated with peripheral inflammation in adipose tissue.…”

Circulating gut microbiota metabolite trimethylamine N‐oxide and oral contraceptive use in polycystic ovary syndrome

“…Prevalence of glucose intolerance, type 2 diabetes, obesity, dyslipidemia and metabolic syndrome are increased in PCOS. [3][4][5][6][7] Alterations of gut microbiota or dysbiosis may affect various host metabolic pathways through microbiota-derived metabolites and can play a role in the development of diabetes, obesity and cardiovascular disease. However, whether this increased cardiovascular risk at young age translates into premature or higher morbidity or mortality later in life is yet to be determined.…”

Risk factors associated with intestinal permeability in an adult population: A systematic review

“…Twenty‐four studies reported on 29 statistically significant biomarkers and association with altered IP . Two studies reported that fasting glucose had a weak positive correlation with IP (Table ).…”

“…Two other liver enzymes aspartate transaminase (AST) and gamma glutamyltransferase were reported to have a weak positive correlation with IP, with only AST reported as an independent risk factor for IP ( β = 0.02; 95% CI: 0.002, 0.037; P = 0.04) . One study reported that microbial diversity had a weak negative correlation with serum zonulin and stool zonulin …”