Enhanced glucose homeostasis via Clostridium symbiosummediated glucagon-like peptide 1 inhibition of hepatic gluconeogenesis in mid-intestinal bypass surgery

BACKGROUND The small intestine is known to play a crucial role in the development and remission of diabetes mellitus(DM).However,the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood.AIM To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism.METHODS Streptozotocin(STZ)was used to induce DM in Sprague-Dawley(SD)rats at a dose of 60 mg/kg.The rats were then randomly divided into two groups:The mid-small intestine bypass(MSIB)group and the sham group(underwent switch laparotomy).Following a 6-wk recovery period post-surgery,the rats underwent various assessments,including metabolic parameter testing,analysis of liver glycogen levels,measurement of key gluconeogenic enzyme activity,characterization of the gut microbiota composition,evaluation of hormone levels,determination of bile acid concentrations,and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor.RESULTS The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism,along with increased hepatic glycogen content.Furthermore,there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase.Importantly,the MSIB group exhibited a substantial increase in the abundances of intestinal Lactobacillus,Clostridium symbiosum,Ruminococcus gnavus,and Bilophila.Moreover,higher levels of secondary bile acids,such as intestinal lithocholic acid,were observed in this group.Remarkably,the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1(GLP-1)at 6 wk postoperatively,highlighting their potential role in glucose regulation.These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota.CONCLUSION The findings of this study demonstrate that the introduction of postoperative intestinal Clostridium symbiosum in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats.This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1,resulting in a favorable modulation of glucose homeostasis.

Differences in metabolic improvement after metabolic surgery are linked to the gut microbiota in non-obese diabetic rats

BACKGROUND Different metabolic/bariatric surgery approaches vary in their effect on weight loss and glucose levels,although the underlying mechanism is unclear.Studies have demonstrated that the gut microbiota might be an important mechanism of improved metabolism after metabolic/bariatric surgery.AIM To investigate the relationship between the improvement in metabolic disturbances and the changes in gut microbiota after gastric or intestinal bypass.METHODS We performed sleeve gastrectomy(SG),distal small intestine bypass(DSIB)or sham surgery in nonobese rats with diabetes induced by 60 mg/kg streptozotocin(STZ-DM).RESULTS The group comparisons revealed that both SG and DSIB induced a reduction in body weight and significant improvements in glucose and lipid metabolism in the STZ-DM rats.Furthermore,DSIB exhibited a stronger glucose-lowering and lipidreducing effect on STZ-DM rats than SG.16S ribosomal RNA gene sequencing revealed the gut abundance of some Lactobacillus spp.increased in both the SG and DSIB groups after surgery.However,the DSIB group exhibited a more pronounced increase in the gut abundance of Lactobacillus spp.compared to the SG group,with more Lactobacillus spp.types increased in the gut.CONCLUSION The gut abundance of Lactobacillus was significantly correlated with the improvement in glycolipid metabolism and the change in serum fibroblast growth factor 21 levels.