Defects in the expression of colonic host defense factors associate with barrier dysfunction induced by a high-fat/high-cholesterol diet.

C. rodentium colitis colonic host defense peptides epithelial damage goblet cells high-fat/high cholesterol diets intestinal permeability mucus layer

Journal

Anatomical record (Hoboken, N.J. : 2007)
ISSN: 1932-8494
Titre abrégé: Anat Rec (Hoboken)
Pays: United States
ID NLM: 101292775

Informations de publication

Date de publication:
05 2023
Historique:
revised: 25 08 2022
received: 07 04 2022
accepted: 11 09 2022
medline: 14 4 2023
pubmed: 6 10 2022
entrez: 5 10 2022
Statut: ppublish

Résumé

The effect of Western diets in the gastrointestinal system is largely mediated by their ability to promote alterations in the immunity and physiology of the intestinal epithelium, and to affect the composition of the commensal microbiota. To investigate the response of the colonic epithelium to high-fat/high-cholesterol diets (HFHCDs), we evaluated the synthesis of host defense factors involved in the maintenance of the colonic homeostasis. C57BL/6 mice were fed an HFHCD for 3 weeks and their colons were evaluated for histopathology, gene expression, and microbiota composition. In addition, intestinal permeability and susceptibility to Citrobacter rodentium were also studied. HFHCD caused colonic hyperplasia, loss of goblet cells, thinning of the mucus layer, moderate changes in the composition of the intestinal microbiota, and an increase in intestinal permeability. Gene expression analyses revealed significant drops in the transcript levels of Muc1, Muc2, Agr2, Atoh1, Spdef, Ang4, Camp, Tff3, Dmbt1, Fcgbp, Saa3, and Retnlb. The goblet cell granules of HFHCD-fed mice were devoid of Relmβ and Tff3, indicating defective production of those two factors critical for intestinal epithelial defense and homeostasis. In correspondence with these defects, colonic bacteria were in close contact with, and invading the epithelium. Fecal shedding of C. rodentium showed an increased bacterial burden in HFHCD-fed animals accompanied by increased epithelial damage. Collectively, our results show that HFHCD perturbs the synthesis of colonic host defense factors, which associate with alterations in the commensal microbiota, the integrity of the intestinal barrier, and the host's susceptibility to enteric infections.

Identifiants

pubmed: 36196983
doi: 10.1002/ar.25083
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1165-1183

Informations de copyright

© 2022 American Association for Anatomy.

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Auteurs

Jennifer Valdes (J)

Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Jessica Gagné-Sansfaçon (J)

Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Vilcy Reyes (V)

Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Anny Armas (A)

Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Gisela Marrero (G)

Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Mitterrand Moyo-Muamba (M)

Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Sheela Ramanathan (S)

Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Nathalie Perreault (N)

Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Subburaj Ilangumaran (S)

Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Nathalie Rivard (N)

Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Louis-Charles Fortier (LC)

Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Alfredo Menendez (A)

Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

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