Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability.
Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability.
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DOI：
10.1136/gut.2008.165886
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发表时间：
2009-08
期刊：
影响因子：
24.5
通讯作者：
Delzenne NM
中科院分区：
文献类型：
--
作者：
Cani PD;Possemiers S;Van de Wiele T;Guiot Y;Everard A;Rottier O;Geurts L;Naslain D;Neyrinck A;Lambert DM;Muccioli GG;Delzenne NM
肥胖和糖尿病小鼠表现出肠通透性增强和代谢性内毒素血症，参与代谢紊乱的发生。我们最近的数据支持的想法，选择性增加双歧杆菌。减少高脂肪饮食引起的代谢性内毒素血症和炎症性疾病的影响。在这里，我们假设肠道微生物群的益生元调节通过涉及胰高血糖素样肽-2（GLP-2）的机制降低肠道通透性，从而改善肥胖和糖尿病期间的炎症和代谢紊乱。研究1：用益生元（Ob-Pre）或非益生元碳水化合物作为对照（Ob-Cell）处理ob/ob小鼠（Ob-CT）。研究2：用GLP-2拮抗剂或盐水处理Ob-CT和Ob-Pre小鼠。研究3：用GLP-2激动剂或盐水处理Ob-CT小鼠。我们评估了肠道微生物群、肠道通透性、肠道肽、肠上皮紧密连接蛋白ZO-1和occludin（qPCR和免疫组织化学）、肝脏和全身炎症的变化。益生元治疗的小鼠表现出较低的血浆脂多糖（LPS）和细胞因子，并减少肝脏表达的炎症和氧化应激标志物。与对照组相比，这种降低的炎症张力与较低的肠通透性和改善的紧密连接完整性相关。益生元增加了内源性促胰高血糖素原衍生肽（GLP-2）的生产，而GLP-2拮抗剂消除了大多数益生元的作用。最后，药理学GLP-2治疗降低了与肥胖相关的肠道通透性、全身和肝脏炎症表型，其程度与益生元诱导的肠道微生物群变化相似。我们发现，选择性肠道微生物群变化控制并增加内源性GLP-2的产生，从而通过GLP-2依赖性机制改善肠道屏障功能，有助于改善肥胖和糖尿病期间的肠道屏障功能。
Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes.
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影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
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影响因子：
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DOI：
10.1152/ajpgi.00024.2006
发表时间：
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影响因子：
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作者：
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作者：
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