Metabolism and Nutrition Research Group, Walloon Excellence in Life sciences and BIOtechnology (WELBIO), Louvain Drug Research Institute, Université catholique de Louvain, B-1200 Brussels, Belgium.
Proc Natl Acad Sci U S A. 2013 May 28;110(22):9066-71. doi: 10.1073/pnas.1219451110. Epub 2013 May 13.
Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
肥胖和 2 型糖尿病的特征是肠道微生物群落改变、炎症和肠道屏障破坏。在肥胖和 2 型糖尿病期间，影响肠道屏障功能的微生物组成和与宿主相互作用的机制尚未阐明。我们最近分离出阿克曼氏菌（Akkermansia muciniphila），这是一种居住在黏液层中的黏液降解细菌。这种细菌的存在与啮齿动物和人类的体重呈负相关。然而，这种细菌在肥胖和代谢紊乱期间的确切生理作用尚不清楚。本研究表明，肥胖和 2 型糖尿病小鼠中阿克曼氏菌的丰度降低。我们还观察到，益生元喂养使阿克曼氏菌丰度正常化，这与代谢谱的改善相关。此外，我们证明阿克曼氏菌治疗可逆转高脂肪饮食引起的代谢紊乱，包括脂肪量增加、代谢性内毒素血症、脂肪组织炎症和胰岛素抵抗。阿克曼氏菌给药增加了控制炎症、肠道屏障和肠道肽分泌的内源性大麻素的肠道水平。最后，我们证明所有这些作用都需要活菌阿克曼氏菌，因为热灭活细胞的治疗不能改善代谢谱或黏液层厚度。总之，本研究为细菌（即阿克曼氏菌）调节宿主与肠道微生物群之间相互作用的复杂机制提供了重要的见解。这些结果还为利用这种人类黏液定植菌预防或治疗肥胖及其相关代谢紊乱提供了依据。
