Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis
Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis
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DOI：
10.1016/j.cmet.2016.06.013
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发表时间：
2016-07-12
期刊：
影响因子：
29
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
膳食纤维对葡萄糖和能量稳态的有益作用早已被描述，主要集中在肠道细菌产生短链脂肪酸。然而，膳食纤维的细菌发酵也产生大量的琥珀酸，迄今为止，还没有研究集中在琥珀酸对宿主代谢的作用。在这里，我们给老鼠喂食富含纤维的食物，发现琥珀酸是盲肠中最丰富的羧酸。膳食琥珀酸盐被确定为肠道代谢（IGN）的底物，这是一个改善葡萄糖稳态的过程。因此，饮食琥珀酸改善野生型小鼠的葡萄糖和胰岛素耐受性，但这些作用在IGN缺陷的小鼠中不存在。传统的小鼠与琥珀酸生产者普雷沃氏菌copri殖民表现出代谢的好处，这可能与琥珀酸激活的IGN。因此，微生物群产生的琥珀酸是一种以前未被怀疑的细菌代谢产物，通过激活IGN改善血糖控制。
Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose homeostasis. Accordingly, dietary succinate improved glucose and insulin tolerance in wild-type mice, but those effects were absent in mice deficient in IGN. Conventional mice colonized with the succinate producer Prevotella copri exhibited metabolic benefits, which could be related to succinate-activated IGN. Thus, microbiota-produced succinate is a previously unsuspected bacterial metabolite improving glycemic control through activation of IGN.