title: Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation.
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.
  
  
  METHODS
  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.
authors.affiliation: Clermont Université, 'Microbe intestin inflammation et Susceptibilité de l'Hôte', UMR1071 Inserm/Université d'Auvergne M2iSH, , Clermont-Ferrand, France.
authors.forename: Margarita
authors.initials: M
authors.lastname: Martinez-Medina
authors.forename: Jérémy
authors.initials: J
authors.lastname: Denizot
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dreux
authors.forename: Frédéric
authors.initials: F
authors.lastname: Robin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Billard
authors.forename: Richard
authors.initials: R
authors.lastname: Bonnet
authors.forename: Arlette
authors.initials: A
authors.lastname: Darfeuille-Michaud
authors.forename: Nicolas
authors.initials: N
authors.lastname: Barnich
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D003424:Crohn Disease / Q000209:etiology; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D019422:Dietary Sucrose / Q000009:adverse effects*; D064806:Dysbiosis / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004926:Escherichia coli / Q000502:physiology*; D004927:Escherichia coli Infections / Q000209:etiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006706:Homeostasis; D054884:Host-Pathogen Interactions; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D064307:Microbiota
chemical_list: D015415:Biomarkers; C470556:Ceacam10 protein, mouse; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019422:Dietary Sucrose
keywords: DIETARY - GASTROINTESTINAL INFECTIONS; GUT INFLAMMATION; IBD BASIC RESEARCH; INTESTINAL BARRIER FUNCTION