Association Between Gut Microbiota And The Pathogenesis Of Polycystic Ovary Syndrome

ObjectivesPolycystic ovary syndrome(PCOS)is a common reproductive endocrine disorder,characterized by hyperandrogenism,oligo-anovulation and polycystic ovary morphology.Irregular menstruations,sub-fertility and hirsutism produce negative influences on patients’ life quality.However,its etiology remains elusive.The interaction between gut microbiota and host involves multiple aspects,such as metabolism,endocrine system and nervous system.Dysbiosis of gut microbiota in PCOS is reported previously.However,it is not clear whether gut microbiota is the consequence or the origin of PCOS.This study is aimed to profile gut microbiota dysbiosis of PCOS and discuss its impact on metabolism,endocrine and reproductive functions.MethodsSprague Dawley(SD)rats were subcutaneously injected with dehydroepiandrosterone(DHEA)to establish a PCOS rat model.Metabolic,endocrine and reproductive functions were assessed.Alterations in the gut microbiota were investigated using next generation sequencing.Then,antibiotics were provided in drinking water to establish pseudo germ-free rats.PCOS phenotype in DHEA-treated pseudo germ-free rats was compared with that in conventionally raised rats.Finally,the disturbed gut microbiota of PCOS rats was transplanted by oral gavage to pseudo germ-free rats.Effects of the disturbed gut microbiota on metabolism,endocrine system and reproductive system were investigated.Potential mechanisms behind these changes were discussed.ResultsFirst,PCOS rats induced by DHEA showed disrupted glucose metabolism,endocrine and reproductive functions.Alpha diversity of the gut microbiota decreased in PCOS rats.Reduced relative abundance of Clostridium sensu stricto,Turicibacter,Anaerofustis and taxa at different levels was observed in PCOS group.Secondly,cleaning out gut microbiota by antibiotic treatment improved the endocrine disorders of DHEA-treated rats.However,impaired glucose tolerance and reproductive function remained.Finally,gut microbiota transplantation from PCOS rats to pseudo germ-free rats initiated glucose intolerance,endocrine disorders and reproductive dysfunctions.At the same time,gene expression in recipient liver showed aberrant glucose metabolism,cholesterol metabolism and immune response.ConclusionsHyperandrogenemia can trigger dysbiosis of gut microbiota.Androgen administration leads to abnormal glucose metabolism and ovarian dysfunction in PCOS independent of gut microbiota.The disordered gut microbiota can induce glucose intolerance,endocrine abnormality and reproductive dysfunction by fecal microbiota transplantation,thus being potentially involved in the pathogenesis of PCOS.