Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn’s disease

Kay Diederen, Jia V. Li, Gillian E. Donachie, Tim G. de Meij, Dirk R. de Waart, Theodorus B. M. Hakvoort, Angelika Kindermann, Josef Wagner, Victoria Auyeung, Anje A. te Velde, Sigrid E. M. Heinsbroek, Marc A. Benninga, James Kinross, Alan W. Walker, Wouter J. de Jonge, Jurgen Seppen

Research output: Contribution to journalArticlepeer-review

Abstract

A nutritional intervention, exclusive enteral nutrition (EEN) can induce remission in patients with pediatric Crohn’s disease (CD). We characterized changes in the fecal microbiota and metabolome to identify the mechanism of EEN. Feces of 43 children were collected prior, during and after EEN. Microbiota and metabolites were analyzed by 16S rRNA gene amplicon sequencing and NMR. Selected metabolites were evaluated in relevant model systems. Microbiota and metabolome of patients with CD and controls were different at all time points. Amino acids, primary bile salts, trimethylamine and cadaverine were elevated in patients with CD. Microbiota and metabolome differed between responders and non-responders prior to EEN. EEN decreased microbiota diversity and reduced amino acids, trimethylamine and cadaverine towards control levels. Patients with CD had reduced microbial metabolism of bile acids that partially normalized during EEN. Trimethylamine and cadaverine inhibited intestinal cell growth. TMA and cadaverine inhibited LPS-stimulated TNF-alpha and IL-6 secretion by primary human monocytes. A diet rich in free amino acids worsened inflammation in the DSS model of intestinal inflammation. Trimethylamine, cadaverine, bile salts and amino acids could play a role in the mechanism by which EEN induces remission. Prior to EEN, microbiota and metabolome are different between responders and non-responders.
Original languageEnglish
Article number18879
Pages (from-to)18879
Number of pages17
JournalScientific Reports
Volume10
DOIs
Publication statusPublished - 3 Nov 2020

Keywords

  • gastronenterology
  • gastrointestinal diseases
  • microbiology
  • DEXTRAN SULFATE SODIUM
  • INTESTINAL MICROBIOTA
  • NMR-SPECTROSCOPY
  • RECEPTOR
  • IDENTIFICATION
  • TGR5
  • L-CARNITINE
  • INFLAMMATORY-BOWEL-DISEASE
  • COLITIS
  • CORTICOSTEROIDS

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