Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits
Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits
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DOI：
10.1016/j.cell.2013.12.016
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发表时间：
2014-01-16
期刊：
影响因子：
64.5
通讯作者：
Mithieux, Gilles
中科院分区：
文献类型：
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作者：
De Vadder, Filipe;Kovatcheva-Datchary, Petia;Mithieux, Gilles
可溶性膳食纤维可促进体重和血糖控制的代谢益处，但其潜在机制尚不清楚。最近的证据表明肠道糖异生（IGN）对葡萄糖和能量稳态具有有益的影响。在这里，我们发现短链脂肪酸 (SCFA) 丙酸和丁酸是由肠道微生物群发酵可溶性纤维产生的，通过互补机制激活 IGN。丁酸盐通过 cAMP 依赖性机制激活 IGN 基因表达，而丙酸盐本身就是 IGN 的底物，通过涉及脂肪酸受体 FFAR3 的肠脑神经回路激活 IGN 基因表达。尽管肠道微生物群组成发生了类似的改变，但在缺乏 IGN 的小鼠中，正常小鼠中 SCFA 或膳食纤维所诱导的体重和血糖控制的代谢益处并不存在。因此，IGN 的调节对于 SCFA 和可溶性纤维相关的代谢益处是必要的。
Soluble dietary fibers promote metabolic benefits on body weight and glucose control, but underlying mechanisms are poorly understood. Recent evidence indicates that intestinal gluconeogenesis (IGN) has beneficial effects on glucose and energy homeostasis. Here, we show that the short-chain fatty acids (SCFAs) propionate and butyrate, which are generated by fermentation of soluble fiber by the gut microbiota, activate IGN via complementary mechanisms. Butyrate activates IGN gene expression through a cAMP-dependent mechanism, while propionate, itself a substrate of IGN, activates IGN gene expression via a gut-brain neural circuit involving the fatty acid receptor FFAR3. The metabolic benefits on body weight and glucose control induced by SCFAs or dietary fiber in normal mice are absent in mice deficient for IGN, despite similar modifications in gut microbiota composition. Thus, the regulation of IGN is necessary for the metabolic benefits associated with SCFAs and soluble fiber.