The Role Of Intestinal Flora Im The Occurrence And Insulin Resistance Of Polycystic Ovary Syndrome And Its Mechanism

Background and objectivePolycystic ovary syndrome is a common endocrine and metabolic disease that causes reproductive dysfunction in reproductive-agewomen.Insulin resistance is considered to be the main pathological basis of reproductive dysfunction and abnormal glucose metabolism in patients with polycystic ovary syndrome.But the prevention and long-term control of polycystic ovary syndrome is still unsatisfactory due to the unclear pathogenesis.With germ-free animals,it has been found that intestinal flora play a causative role in many diseases.Some studies have confirmed that the intestinal flora participates in the occurrence of obesity and insulin resistance,leading to the occurrence of metabolic diseases.Previous study of our group on mice with metabolic syndrome induced by high-fat diet,we found that administering stable Ms-SOD can improve abnormal glucose metabolism and insulin resistance by correcting disordered intestinal flora.Therefore,the aim of this study is to investigate the role of intestinal flora in the occurrence and insulin resistance of polycystic ovary syndrome and its mechanism,and trying to correct intestinal flora by Ms-SOD to block the occurrence of polycystic ovary syndrome.MethodThe 1st experiment:Patients with polycystic ovary syndrome and healthy controls were enrolled.Their blood samples were collected and determined metabolic markers,oxidative stress,intestinal barrier and inflammatory factors.Their fecal specimens were collected for 16s sequencing and intestinal flora analysis.The 2nd experiment:Dividing the C57BL/6J mice into control group,LET group,and LET + antibiotics group randomly.For polycystic ovary syndrome model,the letrozole was intragastric administrated for 35 days.Pair-fed control mice were intragastric administrated by carboxymethyl cellulose for 35 days.Meanwhile,mice in LET + antibiotics group were treated with an oral gavage of antibiotics,and mice in other two groups were treated with an oral gavage of sterile water once a day for 35 days.At the end of the experiment,mice were sacrificed and blood,stool and tissue samples were collected for assays.The 3th experiment:Dividing the C57BL/6J mice into control group,LET group,LET+ CDCA group and LET+GUDCA group randomLy.For polycystic ovary syndrome model,the letrozole was intragastric administrated for 35 days.Pair-fed control mice were intragastric administrated by carboxymethyl cellulose for 35 days.Meanwhile,mice in LET + CDCA group were treated with an oral gavage of CDCA,mice in LET + GUDCA group were treated with an oral gavage of GUDCA,and mice in other two groups were treated with an oral gavage of sterile water once a day for 35 days.At the end of the experiment,mice were sacrificed and blood,stool and tissue samples were collected for assays.The 4th experiment:Dividing the C57BL/6J mice into control group,LET group,and LET + SOD group randomLy,For polycystic ovary syndrome model,the letrozole was intragastric administrated for 35 days.Pair-fed control mice were intragastric administrated by carboxymethyl cellulose for 35 days.Meanwhile,mice in LET + SOD group were treated with an oral gavage of SOD,and mice in other two groups were treated with an oral gavage of sterile water once a day for 35 days.At the end of the experiment,mice were sacrificed and blood,stool and tissue samples were collected for assays.Result1.Polycystic ovary syndrome has obvious glucose metabolism disorder and insulin resistance compared with healthy controls.Polycystic ovary syndrome has increased oxidative stress,damaged intestinal barrier and increased serum TNF-?.The composition and function of intestinal flora has obvious changes in patients with polycystic ovary syndrome.2.Antibiotics cleared intestinal flora in mice with polycystic ovary syndrome can improve ovarian polycystic,reduce serum testosterone,reduce fasting blood glucose,improve insulin resistance and increase serum FGF15.3.Intestinal famesoid X receptor regulated ovarian polycystic in mice with polycystic ovary syndrome.CDCA activated FXR to improve intestinal flora and glucose metabolism.4.Mn-SOD administration could improve the intestinal flora,improve ovarian polycystic,reduce serum testosterone,reduce fasting plasma glucose and fasting plasma insulin,and improve insulin resistance in mice with polycystic ovary syndrome.Conclussion1.Patients with polycystic ovary syndrome have obvious intestinal flora disorder and insulin resistance.2.Intestinal flora affects the occurrence and insulin resistance in polycystic ovary syndrome.3.Intestinal flora leads to the occurrence of polycystic ovary syndrome and disorders of glucose metabolism maybe by FXR pathway.4.Improve intestinal flora can block the occurrence and glucose metabolism disorders in polycystic ovary syndrome.The results suggest that the intestinal flora may be the key to the occurrence and insulin resistance in polycystic ovary syndrome.Restoring the normal intestinal flora may become a new target for the prevention and treatment of polycystic ovary syndrome.