| Objective: To explore the effects of Bifidobacterium lactis Probio-M8 on glucose and lipid metabolism and bile acid-farnesyl X receptor axis in type 2 diabetes mellitus(T2DM)mice.Methods: SPF male C57BL/6J mice aged 6 weeks were selected and induced into T2 DM mouse model by high-fat and high-sugar diet combined with streptozotocin(STZ).Twelve successful diabetic mice were randomly divided into placebo group(high fat and high sugar diet+placebo,n=6),probiotics group(high fat and high sugar diet +Probio-M8 4×109CFU,n=6),and normal mice as control group(normal diet+placebo,n=6),once a day,with oral intervention for 8 weeks.1.Record the weight,food intake and water intake of three groups of mice;Fasting blood glucose(FBG),glucose tolerance(OGTT),glycated albumin(GA),fasting insulin(FINS),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected.2.Total bile acids(TBA)and fibroblast growth factor 15(FGF-15)were measured by ELISA.HE staining was used to observe the morphology of liver and pancreas.RT-PCR was used to determine CYP7A1 m RNA and FXR m RNA in liver and colon.3.The intestinal flora of three groups of mice was analyzed based on the full-length sequencing of 16 S r RNA gene by the third-generation Pacbio SMRT RSII sequencing technology.Results: 1.Compared with the control group,the weight of mice in placebo group decreased significantly,and the food intake and water intake increased significantly(P<0.05);Compared with placebo group,the food intake and water intake of probiotics group decreased significantly,while the weight of mice increased significantly(P<0.05).2.Compared with control mice,FBG,OGTT,GA,TC,TG and LDL-C in placebo group increased significantly(P<0.01),while FINS and HDL-C decreased significantly(P<0.01);Compared with placebo group,FBG(P<0.05),OGTT,GA,TG,TC,LDL-C decreased significantly(P<0.01),FINS and HDL-C increased significantly(P<0.05).3.Compared with the control group,the relative content of Bacteroides nordii in the intestinal tract of mice in placebo group increased,while the relative content of Pseudoflavonifractor capillosus and Oscillibacter valericigenes decreased.Compared with placebo group,probiotics group reduced Bacteroides nordii in intestinal tract,and increased the relative contents of pseudoflavone Pseudoflavonifractor capillosus and Oscillibacter valericigenes.4.Compared with the control group,the levels of TBA,CYP7A1 m RNA in liver and colon in placebo group increased significantly,while the levels of FGF-15,FXRm RNA in liver and colon decreased significantly(P<0.01).Compared with placebo group,the levels of TBA,CYP7A1 m RNA in liver and colon of mice in probiotics group decreased significantly(P<0.01),while FGF-15 and FXRm RNA in liver and colon increased significantly(P<0.05).5.Compared with the control group,the structure of pancreas tissue in placebo group shrank,and its shape was irregular and unclear.Hepatocyte edema and hepatic sinus congestion.Compared with placebo group,probiotics group reduced pancreatic β cell necrosis and vacuole formation,hepatocyte edema and hepatic sinus congestion.Conclusion: 1.Probio-M8 can improve the related indexes of glucose and lipid metabolism in T2 DM mice.Its possible mechanism is to regulate intestinal flora to affect BAs-FXR axis,inhibit the expression of CYP7A1 and up-regulate FGF15 level.2.Probio-M8 reduced the relative content of Bacteroides nordii in T2 DM mice,and increased the relative content of Pseudoflavonifractor capillosus and Oscillibacter valericigenes.3.Probio-M8 improved the morphological changes of pancreas and liver in T2 DM mice,and protected liver and pancreatic tissue. |