NAT MED:你的肠道内居住着一种可以减肥的细菌……
3 小时前
来源：生物探索
近日，来自鲁汶大学、瓦赫宁根大学、赫尔辛基大学的联合研究小组发现，肠道细菌Akkermansia muciniphila对超重和糖尿病动物的肠道提供持久的益处。实验发现，即使在巴氏灭菌后，该细菌对肠屏障的强化作用仍然存在。这项研究结果不仅为治疗糖尿病和肥胖的治疗铺平道路，同时也为心血管疾病和胃肠炎提示新方向。该研究发表于11月28日的Nature Medicine杂志上。 巴氏消毒的A. muciniphila治疗效果更强 研究人员发现，A. muciniphila的活性形式可以减轻肥胖和糖尿病。即使巴氏灭菌后（以高于70℃的温度加热），A. muciniphila仍然能够阻止小鼠疾病的进展。进行巴氏杀菌目的是使细菌失活，但并不消灭细菌或破坏其特性。在失活状态下，A. muciniphila还能够继续有效地对抗疾病，这一结果令研究人员十分惊喜。更令人惊讶的是，巴氏灭菌后这些细菌更加活跃，不仅减轻肥胖和糖尿病，改善血脂异常，还防止这些疾病最初的发展。 该研究小组此前的研究发现A. muciniphila在控制肥胖和代谢疾病（如II型糖尿病）中起着重要作用。对于健康的哺乳动物肠道来说，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。给肥胖小鼠喂以A. muciniphila，在不改变其饮食的情况下，它们体重明显减少，而且其体内II型糖尿病的主要症状——胰岛素抗体水平也降低了。但在当时，研究人员并不清楚A. muciniphila保护效应的具体机制。并且，由于A. muciniphila对氧的敏感性及其生长培养基中的动物源性成分都限制了它在人类疾病治疗中的应用。 细菌外膜中的蛋白质是产生疗效的关键 这次新研究发现，巴氏灭菌的A. muciniphila细菌的出人意料的效应是由于细菌外膜中的蛋白质。该蛋白质——Amuc_1100可以与Toll样受体2相互作用，在加热后保仍持功能。巴氏杀菌使细菌整体失活，但对于功能性膜蛋白没有影响，研究人员认为这种蛋白质增强了肠道屏障，在小鼠实验中产生了治疗效果。分离该蛋白质可以用来开发浓缩形式的药物，用于治疗应激、酒精中毒、肝脏疾病和癌症等因素导致的肠炎。 研究结果还证实，在合成培养基中培养的A. muciniphila，活菌或者经巴氏消毒后使用对于人类来说都是安全的。研究人员已经将他们的研究成果申请了多项专利。此外，一家分公司症正开发扩大生产A. muciniphila细菌及其蛋白质。 参考文献： Pasteurised intestinal bacterium reduces effects of obesity and diabetes 参考文献
我要补充文献
 A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice
文献检索：10.1038/nm.4236
文献期刊：Nature Medicine
Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition1, 2, 3, 4, 5, 6, 7. We previously demonstrated that administration of Akkermansia muciniphila to mice prevents the development of obesity and associated complications8. However, the underlying mechanisms of this protective effect remain unclear. Moreover, the sensitivity of A. muciniphila to oxygen and the presence of animal-derived compounds in its growth medium currently limit the development of translational approaches for human medicine9. We have addressed these issues here by showing that A. muciniphila retains its efficacy when grown on a synthetic medium compatible with human administration. Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidemia in mice. These improvements were notably associated with a modulation of the host urinary metabolomics profile and intestinal energy absorption. We demonstrated that Amuc_1100, a specific protein isolated from the outer membrane of A. muciniphila, interacts with Toll-like receptor 2, is stable at temperatures used for pasteurization, improves the gut barrier and partly recapitulates the beneficial effects of the bacterium. Finally, we showed that administration of live or pasteurized A. muciniphila grown on the synthetic medium is safe in humans. These findings provide support for the use of different preparations of A. muciniphila as therapeutic options to target human obesity and associated disorders. |
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