Effects Of Sleeve Gastrectomy On Gut Microbiota And Fecal Metabolites In Rat Models Of Polycystic Ovary Syndrome

Background:To date,the exact pathogenesis of polycystic ovary syndrome(PCOS)remains uncharacterized.Alterations in the gut microbiota and metabolites have been associated with the development of PCOS.Except for the obese women with PCOS,the non-obese women with PCOS also account for a certain proportion,especially in Asian populations.Sleeve gastrectomy(SG)is a popular bariatric surgical procedure,which may be beneficial for obese women with PCOS.However,the potential mechanisms by which SG improves PCOS remain unknown.Particularly,the changes occurring in the intestinal flora and fecal metabolites with individuals with PCOS following SG need to be elucidated.Moreover,there have been fewer studies on the effects and suitability for non-obese patients with PCOS.In this study,we proposed the following hypotheses:①)SG could modify the intestinal flora and metabolites in individuals with PCOS,and consequently,improves the phenotypes of PCOS.②Some fecal metabolites may be used as prognostic biomarkers of PCOS following SG.Aim:To explore the potential influences of SG on the gut microbiota composition and alterations in the fecal metabolites in rat models of PCOS.Further,we investigated the association among the intestinal flora,the metabolites,and efficacy of SG on the rat models of PCOS.Then,to screen out some fecal metabolites which could be used as prognostic biomarker of PCOS following SG.Methods:Firstly,bioinformatics analysis of bibliometrics were applied to show the research hotspots in the field of PCOS.Secondly,this study was based on the PCOS rat models induced by Dehydroepiandrosterone(DHEA)alone or in combination with a high-fat diet.Thirdly,sleeve gastrectomy was the main intervention.Next,16S RNA gene sequencing technology and metabolomics(Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry,UPLC-MC)were served as the major experimental methods.Finally,the changes of gut microbiota and fecal metabolites following SG were also detected.Then,the correlation analysis was conducted among phenotypes,gut microbiota,and fecal metabolites.Results:First,bibliometric analysis showed that the effects of bariatric surgery on the prognosis of PCOS may become a valuable hot topic in this field.However,there were fewer studies focused on the effects of metabolic surgery on non-obese PCOS individuals.Second,the abundance of Parabacteroides and Odoribacter were high,while Akkermansia was low.Metabolomics analysis showed the abundance of branched chain amino acids(BCAAs)were high,while the abundance of pentadecanoic acid was low in feces of obese PCOS rats.Moreover,tricarboxylic acid cycle(TCA)dysfunction was the main disorder in the metabolic pathway of PCOS.Third,our data showed that SG improved the reproductive and metabolic disorders both in the obese and non-obese PCOS rats.At genus level,the abundance of Firmicutes decreased,while that of Bacteroidetes increased.The abundance of Bacteroides and Blautia increased,but the abundance of Ruminococcus,Clostridium and Alistipes decreased.The abundance of Bifidobacterium increased only in obese PCOS rats.Moreover,SG decreased the contents of butyric acid and isocitric acid in the feces of PCOS rats.Furthermore,SG improved TCA dysfunction in rat models of PCOS.In addition,SG elevated the contents of pentadecanoic acid in the feces of obese PCOS rats.Correlation analysis suggested that the changes of intestinal flora and metabolites following SG were closely related with the improvement of phenotypes in the rats of PCOS.Conclusion and innovation:SG was effective not only for obese PCOS rats,but also for non-obese PCOS rats.Although the diverse effects of SG on the gut microbiota and fecal metabolites in obese and non-obese PCOS rats,the regulation of gut microbiota and metabolites following SG was correlated with the amelioration of phenotypes in PCOS.The present study interpreted the beneficial effects of SG on PCOS from a new perspective of gut microbiota and metabolites.Furthermore,some fecal metabolites which could be served as prognostic biomarkers of PCOS following SG were screened out in this study.