PNAS：调节代谢的肠道菌

　　

生物通报道：肠道是无数细菌居住的复杂生态系统，与多种机体功能有关。研究人员对小鼠的肠道菌进行研究，发现细菌Akkermansia muciniphila在控制肥胖和代谢疾病（如二型糖尿病）中起着重要作用。文章发表在本周的美国国家科学院院刊PNAS杂志上。

在肥胖症和二型糖尿病中，患者体内发生炎症、肠道菌群遭到改变、肠道的屏障受到破坏。对于健康的哺乳动物肠道来说，细菌A. muciniphila占肠道菌的3–5%。但在患有肥胖症或二型糖尿病的人类和小鼠中，这种细菌在肠道内的水平要低得多。鲁汶大学（Catholic University of Louvain）的Patrice Cani一直致力于研究肠道菌与代谢的关系，他领导的这项新研究揭示了肠道菌与人类疾病的关联。

研究人员发现，摄取高脂饮食的小鼠，肠道的A. muciniphila比正常饮食的小鼠少一百倍。他们随即给这些小鼠喂食活A. muciniphila，并通过饮食促进肠道菌的生长，由此将小鼠肠道的A. muciniphila恢复到正常水平。

研究显示，上述措施产生了显著的效果。与对照组相比，小鼠的体重减轻，脂肪量更少，肠道粘液层更厚，胰岛素抵抗得到缓解。此外，其他许多与肥胖和代谢疾病相关的指标也得到了改善。文章总结道，A. muciniphila的丰度正常化，可以改善代谢谱，逆转高脂饮食诱发的代谢紊乱。

“我们在疾病相关的各种参数之间寻找共同的因素，”Cani说。

研究团队随后进行了深入研究，以阐明细菌影响代谢的复杂机制。研究显示，使A. muciniphila重回正常水平的措施，增加了肠道中内源性大麻素（endocannabinoid）的水平，而这一信号分子可以帮助机体控制血糖水平，并且协助肠道抵御有害微生物。

研究人员还指出，A. muciniphila与肠道壁细胞和免疫系统均有交流。该细菌能够发出信号影响抗菌分子的合成，并同时增加肠道的粘液。

Cani坚信，未来A. muciniphila将有望用于治疗肥胖症、糖尿病和结肠炎等疾病。“已有许多证据将这种细菌与人类疾病联系起来，”他说。不过，这项研究用于临床治疗还需要时日，人们首先需要找到改变肠道菌群的最佳方式。

这项研究向人们展示了肠道菌与宿主间的相互交流，有助于进一步认识细菌调控的复杂机制。研究人员指出，在A. muciniphila与机体相互作用时还涉及了免疫系统，在此基础上人们或许能够找到出操纵肠道菌的新途径。

 

（生物通编辑：叶予）

生物通推荐原文摘要：

Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity

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.