title: Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis.
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.
authors.affiliation: 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.
authors.forename: Filipe
authors.initials: F
authors.lastname: De Vadder
authors.affiliation: Wallenberg Laboratory and Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
authors.forename: Petia
authors.initials: P
authors.lastname: Kovatcheva-Datchary
authors.affiliation: 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.
authors.forename: Carine
authors.initials: C
authors.lastname: Zitoun
authors.affiliation: 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.
authors.forename: Adeline
authors.initials: A
authors.lastname: Duchampt
authors.affiliation: 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.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
authors.affiliation: 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.
authors.forename: Gilles
authors.initials: G
authors.lastname: Mithieux
mesh_terms: D000818:Animals; D002432:Cecum / Q000187:drug effects / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D005838:Genotype; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects; D009844:Oligosaccharides / Q000494:pharmacology; D018720:Prevotella / Q000187:drug effects / Q000378:metabolism; D019802:Succinic Acid / Q000494:pharmacology*
chemical_list: D009844:Oligosaccharides; C116580:fructooligosaccharide; D019802:Succinic Acid; D005947:Glucose