Metabolism and T2D: liraglutide influences glucose metabolism and inflammation through gut microbiota

Liraglutide targets the gut microbiota and the glucolipid metabolism to regulate insulin secretion

Charpentier and colleagues showed that Liraglutide targets the gut microbiota and the glucolipid metabolism to regulate insulin secretion:


→ T2D is characterized by low-grade inflammation which prevents insulin secretion and action, and is associated with gut microbiota dysbiosis, also a major factor in low-grade inflammation.

→ No T2D treatment regulates low-grade inflammation and gut microbiota dysbiosis.

→ In an HFD mouse model, liraglutide improved glucolipid metabolism and glucose-induced insulin secretion. Liraglutide was also associated with changes in the gut microbiota composition and intestinal immune cell phenotypes.

→ These beneficial effects were suppressed by antibiotic treatment and reproduced by FMT from liraglutide-treated mice to germ-free mice, showing that liraglutide specifically affects the gut microbiota, which controls, at least in part, glucose-induced insulin secretion.


Tissue microbiomes_1


Liraglutide targets the gut microbiota and the intestinal immune system to regulate insulin secretion


➔ In collaboration with Vaiomer

Charpentier J, Briand F, Lelouvier B, Servant F, Azalbert V, Puel A, Christensen JE, Waget A, Branchereau M, Garret C, Lluch J, Heymes C, Brousseau E, Burcelin R, Guzylack L, Sulpice T, Grasset E. Acta Diabetol. 2021 Jul;58(7):881-897. doi: 10.1007/s00592-020-01657-8. Epub 2021 Mar 15. PMID: 33723651.

Liraglutide controls type 2 diabetes (T2D) and inflammation. Gut microbiota regulates the immune system and causes at least in part type 2 diabetes. We here evaluated whether liraglutide regulates T2D through both gut microbiota and immunity in dysmetabolic mice.

Diet-induced dysmetabolic mice were treated for 14 days with intraperitoneal injection of liraglutide (100 μg/kg) or with vehicle or Exendin 4 (10 μg/kg) as controls. Various metabolic parameters, the intestinal immune cells were characterized and the 16SrDNA gene sequenced from the gut. The causal role of gut microbiota was shown using large spectrum antibiotics and by colonization of germ-free mice with the gut microbiota from treated mice.

Besides, the expected metabolic impacts liraglutide treatment induced a specific gut microbiota specific signature when compared to vehicle or Ex4-treated mice. However, liraglutide only increased glucose-induced insulin secretion, reduced the frequency of Th1 lymphocytes, and increased that of TReg in the intestine. These effects were abolished by a concomitant antibiotic treatment. Colonization of germ-free mice with gut microbiota from liraglutide-treated diabetic mice improved glucose-induced insulin secretion and regulated the intestinal immune system differently from what observed in germ-free mice colonized with microbiota from non-treated diabetic mice.

Altogether, our result demonstrated first the influence of liraglutide on gut microbiota and the intestinal immune system which could at least in part control glucose-induced insulin secretion.


Keywords: Germ-free mice; Intestinal immune system; Metabolic diseases; Microbiota

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