Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis

TY - JOUR

T1 - Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis

AU - De Vadder, Filipe

AU - Kovatcheva-Datchary, Petia

AU - Zitoun, Carine

AU - Duchampt, Adeline

AU - Bäckhed, Gert Fredrik

AU - Mithieux, Gilles

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/7/12

Y1 - 2016/7/12

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.cmet.2016.06.013

DO - 10.1016/j.cmet.2016.06.013

M3 - Journal article

C2 - 27411015

SN - 1550-4131

VL - 24

SP - 151

EP - 157

JO - Cell Metabolism

JF - Cell Metabolism

IS - 1

ER -