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Nat Commun. 2015 Aug 4;6:7806. doi: 10.1038/ncomms8806.

Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model.

Author information

1
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.
2
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2P5.
3
Molecular Microbial Pathogenesis Unit, Institut Pasteur, Paris 75724, France.
4
The UVic-Genome British Columbia Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada V8Z 7X8.
5
Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
6
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
7
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.
8
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.

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.

Comment in

PMID:
26241678
PMCID:
PMC4532793
DOI:
10.1038/ncomms8806
[Indexed for MEDLINE]
Free PMC Article

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