Intestinal Microbiota Plays A Role In The Diabetogenic Effects Of Immunosuppressor Tacrolimus In Mice

Both immunosuppressors and antibiotics are indispensable for transplant patients.However,the former increases risk of new onset diabetes,whereas the latter impacts intestinal microbiota.It is still unclear whether and how interaction between im1unosuppressors and antibiotics alters the intestinal microbiota and thus leads to metabolic disorder of glucose.This study examined alterations of glucose and lipid metabolism and intestinal microbiota in mice exposure to tacrolimus with or without antibiotics.We found that tacrolimus-induced glucose toleranee was further aggravated by antibiotics,although they improved insulin secretion.Combined treatment resulted in exacerbated lipid accumulation in the liver.Alteration of microbial community related to tacrolimus was further amplified by antibiotics administration,which was characterized by the reduction trend of tacrolimus on phylum Firlicutes,and its family Lachnospiraceae,genus Coprococous.Analyses based on the metagenomics profiles revealed that antibiotics augmented the effect of tacrolimus on lipid metabolism-related function of microbiota.The altered gut microbiome and predicted microbial functional profiles were significantly correlated with the hepatic lipid accumulation and glucose disorders,respectively.In conclusion,antibiotics aggravated the effect of tacrolimus on microbiome and its metabolic capacities,which might contribute to hepatic lipid accumulation and glucose disorders.These findings suggest that altered microbiome by antibiotics can amplify the diabetogenic effect of tacrolimus,and might be a novel therapeutic target for patients.