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Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation
  1. Margarita Martinez-Medina1,2,3,
  2. Jérémy Denizot1,2,
  3. Nicolas Dreux1,2,
  4. Frédéric Robin1,2,4,
  5. Elisabeth Billard1,2,5,
  6. Richard Bonnet1,2,4,
  7. Arlette Darfeuille-Michaud1,2,4,5,
  8. Nicolas Barnich1,2,5
  1. 1Clermont Université, ‘Microbe intestin inflammation et Susceptibilité de l'Hôte’, UMR1071 Inserm/Université d'Auvergne M2iSH, Clermont-Ferrand, France
  2. 2Unité sous contrat Institut National de la Recherche Agronomique 2018, Clermont-Ferrand, France
  3. 3Laboratory of Molecular Microbiology, Biology Department, University of Girona, Girona, Spain
  4. 4Laboratoire de Bactériologie Clinique, Centre Hospitalier de Clermont-Ferrand, Clermont-Ferrand, France
  5. 5Génie Biologique, Institut Universitaire de Technologie, Aubière, France
  1. Correspondence to Dr Nicolas Barnich, Clermont Université, M2iSH, Microbe intestin inflammation et Susceptibilité de l'Hôte, Inserm/Université d'Auvergne UMR 1071, CBRV, 28 place Henri Dunant, Clermont-Ferrand 63001, France; nicolas.barnich{at}udamail.fr

Abstract

Objective Western diet is a risk factor for Crohn's disease (CD). Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is abnormally expressed in CD patients. This allows adherent-invasive Escherichia coli (AIEC) to colonise the gut mucosa and leads to inflammation. We assessed the effects of a high fat/high sugar (HF/HS) Western diet on gut microbiota composition, barrier integrity and susceptibility to infection in transgenic CEABAC10 mice expressing human CEACAMs.

Design Colonic microbiota composition and susceptibility of CEABAC10 mice to AIEC LF82 bacteria infection were determined in mice fed a conventional or HF/HS diet. Barrier function and inflammatory response were assessed by studying intestinal permeability, tight junction protein and mucin expression and localisation, and by determining histological score and levels of cytokine release.

Results HF/HS diet led to dysbiosis in WT and transgenic CEABAC10 mice, with a particular increase in E coli population in HF/HS-fed CEABAC10 mice. These mice showed decreased mucus layer thickness, increased intestinal permeability, induction of Nod2 and Tlr5 gene transcription, and increased TNFα secretion. These modifications led to a higher ability of AIEC bacteria to colonise the gut mucosa and to induce inflammation.

Conclusions Western diet induces changes in gut microbiota composition, alters host homeostasis and promotes AIEC gut colonisation in genetically susceptible mice. These results support the multifactorial aetiology of CD and highlight the importance of diet in CD pathogenesis.

  • DIETARY - GASTROINTESTINAL INFECTIONS
  • IBD BASIC RESEARCH
  • INTESTINAL BARRIER FUNCTION
  • GUT INFLAMMATION

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