Gut Commensal E. coli Proteins Activate Host Satiety Pathways following Nutrient-Induced Bacterial Growth
Gut Commensal E. coli Proteins Activate Host Satiety Pathways following Nutrient-Induced Bacterial Growth
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DOI：
10.1016/j.cmet.2015.10.017
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发表时间：
2016-02-09
期刊：
影响因子：
29
通讯作者：
Fetissov, Serguei O.
中科院分区：
文献类型：
--
作者：
Breton, Jonathan;Tennoune, Naouel;Fetissov, Serguei O.
肠道微生物区系的组成与宿主的代谢表型有关，但尚不清楚肠道细菌是否会影响宿主的食欲。在这里，我们表明，有规律的营养供应稳定了大肠杆菌的指数增长，在提供营养后20分钟出现了静止阶段，伴随着细菌蛋白质组的变化，这表明细菌蛋白质参与了宿主的饱腹感。事实上，肠道注射大肠杆菌固定相蛋白增加了血浆PYY，它们的腹腔注射严重抑制了食物的摄取，激活了下丘脑POMC神经元中的c-Fos，而它们的重复给药减少了食物的量。ClpB是一种模拟α-MSH的细菌蛋白，在大肠杆菌固定相上调，在血浆中检测到与粪便中ClpB DNA成正比，并刺激下丘脑POMC神经元的放电频率。因此，这些数据表明，营养诱导的大肠杆菌生长后产生的细菌蛋白可能是终止进餐的信号。此外，持续接触大肠杆菌蛋白质可能会影响长期的饮食模式。
The composition of gut microbiota has been associated with host metabolic phenotypes, but it is not known if gut bacteria may influence host appetite. Here we show that regular nutrient provision stabilizes exponential growth of E. coli, with the stationary phase occurring 20 min after nutrient supply accompanied by bacterial proteome changes, suggesting involvement of bacterial proteins in host satiety. Indeed, intestinal infusions of E. coli stationary phase proteins increased plasma PYY and their intraperitoneal injections suppressed acutely food intake and activated c-Fos in hypothalamic POMC neurons, while their repeated administrations reduced meal size. ClpB, a bacterial protein mimetic of alpha-MSH, was upregulated in the E. coli stationary phase, was detected in plasma proportional to ClpB DNA in feces, and stimulated firing rate of hypothalamic POMC neurons. Thus, these data show that bacterial proteins produced after nutrient-induced E. coli growth may signal meal termination. Furthermore, continuous exposure to E. coli proteins may influence long-term meal pattern.