title: Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model.
abstract: Environmental enteropathy (EE) is a subclinical chronic inflammatory disease of the small intestine and has a profound impact on the persistence of childhood malnutrition worldwide. However, the aetiology of the disease remains unknown and no animal model exists to date, the creation of which would aid in understanding this complex disease. Here we demonstrate that early-life consumption of a moderately malnourished diet, in combination with iterative oral exposure to commensal Bacteroidales species and Escherichia coli, remodels the murine small intestine to resemble features of EE observed in humans. We further report the profound changes that malnutrition imparts on the small intestinal microbiota, metabolite and intraepithelial lymphocyte composition, along with the susceptibility to enteric infection. Our findings provide evidence indicating that both diet and microbes combine to contribute to the aetiology of EE, and describe a novel murine model that can be used to elucidate the mechanisms behind this understudied disease.
authors.affiliation: 1] Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada [2] Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Brown
authors.affiliation: 1] Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada [2] Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Marta
authors.initials: M
authors.lastname: Wlodarska
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2P5.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Willing
authors.affiliation: Molecular Microbial Pathogenesis Unit, Institut Pasteur, Paris 75724, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Vonaesch
authors.affiliation: The UVic-Genome British Columbia Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada V8Z 7X8.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Lisa A
authors.identifier: 0000000229692296
authors.initials: LA
authors.lastname: Reynolds
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Marie-Claire
authors.identifier: 0000000244903370
authors.initials: MC
authors.lastname: Arrieta
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Marco
authors.initials: M
authors.lastname: Uhrig
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Roland
authors.initials: R
authors.lastname: Scholz
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Partida
authors.affiliation: 1] The UVic-Genome British Columbia Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada V8Z 7X8 [2] Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada V8P 5C2.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Borchers
authors.affiliation: Molecular Microbial Pathogenesis Unit, Institut Pasteur, Paris 75724, France.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
authors.affiliation: 1] Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada [2] Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4 [3] Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
mesh_terms: D000818:Animals; D001439:Bacteroides; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D004926:Escherichia coli; D005260:Female; D006128:Growth; D007410:Intestinal Diseases / Q000378:metabolism / Q000382:microbiology*; D007421:Intestine, Small / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D008214:Lymphocytes / Q000502:physiology; D044342:Malnutrition / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D055442:Metabolome; D008810:Mice, Inbred C57BL; D064307:Microbiota; D011897:Random Allocation