Dysbiosis Of Gut Microbiota In Polycystic Ovary Syndrome And Related Clinical Intervention

Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects about 6.7% woman around the world.The major features are excessive androgen secretion,chronic anovulation and polycystic ovaries.A large proportion of PCOS patients have obesity,insulin resistance,dyslipidemia and chronic systemic low-grade inflammation.Gut microbiota acts as a “forgotten organ” and has a closely relation to the development of host chronic inflammation and metabolic disorders.It suggests that the development of PCOS may have a correlation with dysbiosis of intestinal flora.Diet change is one of the first-line treatments of PCOS,and gut microbiota may be the intermediary between dietary intervention and clinical improvement of PCOS.Acarbose inhibits alpha glucosidase,an intestinal enzyme that releases glucose from larger carbohydrates.More carbohydrates arrive at colon and can be used as nutrition by the probiotics.In this study,we investigated dysbiosis of gut microbiota of PCOS and the ameliorative effect by gut microbiota-targeted dietary intervention and acarbose.First,there were 33 patients with PCOS(non-obese PCOS individuals,PN,n=12;obese PCOS individuals,PO,n=21)as well as 15 control subjects(non-obese control individuals,CN,n=9;obese control individuals,CO,n=6)enrolled in our study.The plasma levels of serotonin,ghrelin and peptide YY(PYY)were significantly decreased in patients with PCOS compared with controls,and have a significantly negative correlation with waist circumference and testosterone.Sequencing of the V3-V4 region of the 16 S rRNA gene in fecal samples revealed the substantial differences of gut microbial species between the PCOS and non-obese controls.Bacterial species were clustered into 23 co-abundance groups(CAGs)based on the SparCC correlation coefficients of their relative abundance.The CAGs increased in PCOS,including the bacteria belonging to Bacteroides,Escherichia/Shigella and Streptococcus,were negatively correlated with ghrelin,and positively correlated with testosterone and BMI.Furthermore,the CAGs that were decreased in PCOS,including the bacteria from Akkermansia and Ruminococcaceae,showed opposite relationship with body-weight,sex-hormone and brain-gut peptides.In conclusion,gut microbial dysbiosis in women with PCOS is associated with the disease phenotypes.Then,we designed a high-fiber dietary scheme based on whole grains,traditional Chinese medicinal foods and prebiotics(WTP diet).Thirty-three PCOS patients were recruited and they were randomly divided into WTP and APW groups.Finally 12 individuals in the APW group and 17 in the WTP group completed the 12-week intervention.Both of the two intervention methods improved the obesity and insulin resistance related parameters.The composition of gut microbiota also changed.Probiotics Bifidobacterium and Lactobacillus increased after intervention.Intervention of APW group reduced serum testosterone and LH/FSH significantly.It indicated that acarbose improved the clinical symptoms of PCOS.The structures of gut microbiota also showed differences between two groups.Acarbose inhibited host's absorption of saccharides and more carbohydrate entered large intestine utilized by gut microbiota.Abovementioned process might explain how acarbose changed the structure of gut microbiota.Fecal water contains a range of bioactive components which derived from dietary sources,human host and gut bacteria.It has been proposed as a biomarker to assess the effect that specific dietary components have on chronic disease risks.In this study,both intervention methods decreased cytotoxicity of fecal water.Isobutyric acid,valeric acid and isovaleric acid decreased significantly.The pH of fecal water showed a declining trend.This study suggested a correlation between the alteration of gut microbiota and the improvement of clinical parameters.These results preliminarily showed that gut microbiota may participate in the development of PCOS.Thus,gut microbiota become a treatment target of PCOS related symptoms.This study laid a foundation of research on the pathogenesis of PCOS,and also provided a basis on gut microbiota targeted clinically dietary intervention.