The Role Of Gut Microbiota On Pancreatic ? Cell Function In TLR4 Deficient Obese Mice

Objective Gut microbiota which participate in the metabolism of the body as well as immune process,is closely associated with diabetes.The aim of this research is to explore the effect of gut microbiota on insulin resistance and ? cell function in TLR4 deficient obese mice.Methods TLR4 deficient C57BL/10ScN(KO)and its homologous control(WT)mice were fed with HFD(60 kcal%)for 12 weeks.Blood glucose was detected by Accu-Chek blood glucose meter,and insulin was detected by hypersensitive mouse insulin ELISA kit.Short chain fatty acids were detected by mass spectrometry.Colonic contents,mucosa and pancreatic flora were detected by 16 S rDNA high-throughput sequencing.Results The overall structure of gut microbiota in colonic content and mucosa are similar.Firstly,TLR4 deficiency increased insulin sensitivity and glucose stimiluted insulin secretion,and increased SCFAs concentration as well.In addition,the abundance of probiotics increased and that of opportunity pathogens decreased in KO mice.The changes of these bacteria were negatively correlated with parameters related to insulin resistance,and were positively correlated with those related to ? cell function.Pancreatic bacteria were different with gut bacteria,and the latter seldom exist in pancreas.At last,intestinal proteomics showed 880 differentially expressed proteins,380 of which were up-regulated and 500 down-regulated.Probiotics and SCFAs were positively correlated with intestinal anti-inflammatory proteins,positively correlated with antioxidant enzymes,and opportunistic pathogens were negatively correlated with antioxidant enzymes.Conclusion TLR4 knockout can improve glucose secretion in obese mice by increasing the abundance of intestinal probiotics and increasing SCFAs concentration.