The Study Of Changes Of Intestinal Microbe And Intestinal Barrier In Obese Type 2 Diabetic Mice After Bariatric Surgery

ObjectiveAfter duodenal jejunal Y bypass(DJYB)in obese type 2 diabetic mice,16 sr RNA metagenomics sequencing was used to investigate the correlation between the changes of gut microbiota in the biliary pancreas limb,digestive limb and common limb and the improvement of blood glucose.In addition,intestinal permeability and barrier related inflammatory factors and protein changes were analyzed after DJYB surgery.MethodC57bl/6J mice were fed a 60%kcal high-fat diet for 6 weeks followed by intraperitoneal injection of streptozotocin(40mg/Kg)to induce type 2 diabetes.22 obese mice with type 2 diabetes were randomly assigned to DJYB group(n=15)and Sham group(n=7).Weight,food intake,random blood glucose were measured before and after surgery.Oral glucose tolerance test were measured at 8 weeks after surgery.The intestinal contents of the biliopancreatic limb,digestive limb and common limb were collected 8 weeks after surgery for 16 sr RNA metagenomics sequencing and transcriptome sequencing.The expressions of IL-1β,IL-6,TNF-α,ZO-1 and claudin-5 in each intestine were detected.ResultsThe random blood glucose of DJYB group was 21.04±2.95mmol/L before surgery and9.3±2.21mmol/L at 8 weeks after surgery,showing statistically significant differences compared with sham group(P < 0.01),but there was no statistically significant difference in weight and food intake between the two groups before and after surgery(P > 0.05).At the level of bacteria,the abundance of Lactobacillus in biliopancreatic limb,digestive limb and common limb in DJYB group was lower than that in sham group,and the abundance of Dubosiella and Faecalibaculum was higher than that in sham group.Compared with sham group,there were no significant differences in the expression levels of IL-1β and IL-6 in biliary and pancreatic limbs of DJYB group(P > 0.05),but the expression levels of IL-1βand IL-6 in digestive and common limbs were significantly decreased(P < 0.05).Compared with sham group,the expression level of TNF-α in biliopancreatic limb,digestive limb and common limb of DJYB group was significantly decreased(P < 0.05).Compared with sham group,there were significant differences in the expressions of ZO-1and claudin 5 in biliopancreatic limbs of DJYB group(P < 0.05).ZO-1 expression was significantly increased in DJYB group(P < 0.01),while claudin 5 expression was not statistically significant.Claudin 5 expression was significantly increased in DJYB group(P< 0.05),and ZO-1 expression was not statistically significant.ConclusionPostoperative improvement of DJYB blood glucose metabolism in diet-induced obesity(DIO)diabetic mice was independent of changes in body weight and food intake,and may be related to changes in bacterial community in different intestinal segments.After DJYB surgery,IL-1β,IL-6 and TNF-α inflammatory factors were reduced and intestinal tight junction proteins ZO-1 and claudin-5 were increased,which reduced intestinal chronic inflammation and jointly maintained intestinal barrier function.