Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity
Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity
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DOI：
10.1073/pnas.1219451110
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发表时间：
2013-05-28
影响因子：
11.1
通讯作者：
Cani, Patrice D.
中科院分区：
文献类型：
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作者：
Everard, Amandine;Belzer, Clara;Cani, Patrice D.
肥胖和2型糖尿病的特征是肠道微生物区系改变、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的相互作用机制尚未阐明。我们最近分离到了粘液阿克曼西亚，这是一种驻留在粘液层的粘蛋白降解菌。在啮齿动物和人类中，这种细菌的存在与体重成反比。然而，这种细菌在肥胖和代谢紊乱中扮演的确切生理角色尚不清楚。这项研究表明，在肥胖和2型糖尿病小鼠中，粘液嗜酸杆菌的丰度降低。我们还观察到，益生素喂养使粘液隐孢子虫的丰度正常化，这与改善代谢状况有关。此外，我们还证明了粘虫治疗逆转了高脂饮食诱导的代谢紊乱，包括脂肪质量增加、代谢性内毒素血症、脂肪组织炎症和胰岛素抵抗。嗜粘菌可增加肠道内源性大麻素的水平，从而控制炎症、肠道屏障和肠肽分泌。最后，我们证明了所有这些作用都需要存活的粘液杆菌，因为用热灭活细胞治疗并不能改善新陈代谢或粘液层厚度。总之，这项研究为细菌(即嗜粘杆菌)调节宿主和肠道微生物区系之间的串扰提供了实质性的洞察力。这些结果也为开发一种使用这种人类粘液定殖物来预防或治疗肥胖及其相关代谢紊乱的治疗方法提供了理论基础。
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.