生物通報道：腸道是無數細菌居住的復雜生態系統，與多種機體功能有關。研究人員對小鼠的腸道菌進行研究，發現細菌Akkermansia muciniphila在控制肥胖和代謝疾病（如二型糖尿病）中起著重要作用。文章發表在本周的美國國家科學院院刊PNAS雜志上。

在肥胖癥和二型糖尿病中，患者體內發生炎癥、腸道菌群遭到改變、腸道的屏障受到破壞。對于健康的哺乳動物腸道來說，細菌A. muciniphila占腸道菌的3–5%。但在患有肥胖癥或二型糖尿病的人類和小鼠中，這種細菌在腸道內的水平要低得多。魯汶大學（Catholic University of Louvain）的Patrice Cani一直致力于研究腸道菌與代謝的關系，他領導的這項新研究揭示了腸道菌與人類疾病的關聯。

研究人員發現，攝取高脂飲食的小鼠，腸道的A. muciniphila比正常飲食的小鼠少一百倍。他們隨即給這些小鼠喂食活A. muciniphila，并通過飲食促進腸道菌的生長，由此將小鼠腸道的A. muciniphila恢復到正常水平。

研究顯示，上述措施產生了顯著的效果。與對照組相比，小鼠的體重減輕，脂肪量更少，腸道粘液層更厚，胰島素抵抗得到緩解。此外，其他許多與肥胖和代謝疾病相關的指標也得到了改善。文章總結道，A. muciniphila的豐度正常化，可以改善代謝譜，逆轉高脂飲食誘發的代謝紊亂。

“我們在疾病相關的各種參數之間尋找共同的因素，”Cani說。

研究團隊隨后進行了深入研究，以闡明細菌影響代謝的復雜機制。研究顯示，使A. muciniphila重回正常水平的措施，增加了腸道中內源性大麻素（endocannabinoid）的水平，而這一信號分子可以幫助機體控制血糖水平，并且協助腸道抵御有害微生物。

研究人員還指出，A. muciniphila與腸道壁細胞和免疫系統均有交流。該細菌能夠發出信號影響抗菌分子的合成，并同時增加腸道的粘液。

Cani堅信，未來A. muciniphila將有望用于治療肥胖癥、糖尿病和結腸炎等疾病。“已有許多證據將這種細菌與人類疾病聯系起來，”他說。不過，這項研究用于臨床治療還需要時日，人們首先需要找到改變腸道菌群的最佳方式。

這項研究向人們展示了腸道菌與宿主間的相互交流，有助于進一步認識細菌調控的復雜機制。研究人員指出，在A. muciniphila與機體相互作用時還涉及了免疫系統，在此基礎上人們或許能夠找到出操縱腸道菌的新途徑。

（生物通編輯：葉予）

生物通推薦原文摘要：

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.