Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis

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  • Filipe De Vadder
  • Petia Kovatcheva-Datchary
  • Carine Zitoun
  • Adeline Duchampt
  • Gert Fredrik Bäckhed
  • Gilles Mithieux

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.

Original languageEnglish
JournalCell Metabolism
Volume24
Issue number1
Pages (from-to)151-7
Number of pages7
ISSN1550-4131
DOIs
Publication statusPublished - 12 Jul 2016

    Research areas

  • Journal Article

ID: 166682234