Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.
Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Paul Sabatier (UPS), Team 2: 'Intestinal Risk Factors Diabetes, Dyslipidemia', 31432, Toulouse Cedex 4, France.
Acta Diabetol. 2021 Jul;58(7):881-897. doi: 10.1007/s00592-020-01657-8. Epub 2021 Mar 15.
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.
利拉鲁肽可控制 2 型糖尿病（T2D）和炎症。肠道微生物群调节免疫系统，并至少部分导致 2 型糖尿病。我们在此评估利拉鲁肽是否通过肠道微生物群和免疫来调节代谢异常小鼠的 T2D。
用腹腔注射利拉鲁肽（100μg/kg）或载体或 Exendin 4（10μg/kg）治疗饮食诱导的代谢异常小鼠 14 天。描述各种代谢参数、肠道免疫细胞，并对肠道的 16SrDNA 基因进行测序。使用广谱抗生素和用来自治疗小鼠的肠道微生物群定植无菌小鼠来显示肠道微生物群的因果作用。
除了预期的代谢影响外，与载体或 Ex4 处理的小鼠相比，利拉鲁肽处理还诱导了特定的肠道微生物群特征。然而，利拉鲁肽仅增加了葡萄糖诱导的胰岛素分泌，减少了 Th1 淋巴细胞的频率，并增加了肠道中的 TReg 频率。这些作用被同时的抗生素治疗所消除。用来自利拉鲁肽治疗的糖尿病小鼠的肠道微生物群定植无菌小鼠改善了葡萄糖诱导的胰岛素分泌，并调节了肠道免疫系统，与用未治疗的糖尿病小鼠的肠道微生物群定植的无菌小鼠观察到的不同。
总之，我们的结果首次证明了利拉鲁肽对肠道微生物群和肠道免疫系统的影响，这至少部分可以控制葡萄糖诱导的胰岛素分泌。
