Liraglutide targets gut-microbiota and the intestinal immune system to regulate glycemia

Since a gut microbiota-mediated metabolic inflammation characterizes type 2 diabetic patients, we here evaluated the impact of Liraglutide on gut microbiota and the immune system in rodent models. Diet-induced dysmetabolic mice were treated chronically with intraperitoneal injection of vehicle, Exendin 4 (10µg/kg) or Liraglutide (100µg/kg) for 14 days. The data show that Exendin 4 and Liraglutide induced a significant body weight loss, improved the glucose tolerance, reduced triglyceride levels and intestinal cholesterol absorption and increased cholesterol fecal excretion when compare to vehicle. Significant changes in Bifidobacteriaceae, Clostridiaceae or Lactobaciliceae were observed in the feces. Following Liraglutide treatment, the frequency of Th1 lymphocytes was reduced while the frequency of TReg lymphocytes was increased in the intestine and these effects were abolished by concomitant antibiotic treatment. The colonizsation with the ileum microbiota from Liraglutide-treated mice improved the glycemic control when compared to germ-free mice colonized with gut microbiota from vehicle-treated mice. Altogether, we showed that Liraglutide alters gut microbiota improving the intestinal adaptive immune system which could explain the anti-diabetic effects of the GLP-1 receptor agonist.