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Cell Metab. 2016 Jul 12;24(1):151-7. doi: 10.1016/j.cmet.2016.06.013.

Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis.

Author information

1
Institut National de la Santé et de la Recherche Médicale, U1213, Lyon 69372, France; Université de Lyon, Lyon 69008, France; Université Lyon 1, Villeurbanne 69622, France; Wallenberg Laboratory and Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
2
Wallenberg Laboratory and Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
3
Institut National de la Santé et de la Recherche Médicale, U1213, Lyon 69372, France; Université de Lyon, Lyon 69008, France; Université Lyon 1, Villeurbanne 69622, France.
4
Wallenberg Laboratory and Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark. Electronic address: fredrik.backhed@wlab.gu.se.
5
Institut National de la Santé et de la Recherche Médicale, U1213, Lyon 69372, France; Université de Lyon, Lyon 69008, France; Université Lyon 1, Villeurbanne 69622, France. Electronic address: gilles.mithieux@inserm.fr.

Abstract

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.

PMID:
27411015
DOI:
10.1016/j.cmet.2016.06.013
[Indexed for MEDLINE]
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