Unique dietary-related mouse model of colitis

Harris Bernstein, Hana Holubec, Carol Bernstein, Natalia Ignatenko, Eugene Gerner, Katerina Dvorak, David Besselsen, Lois Ramsey, Monique Dall'Agnol, Karen Ann Blohm-Mangone, Jose Padilla-Torres, Haiyan Cui, Harinder Garewal, Claire Margaret Payne

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31 Scopus citations

Abstract

Background: A high-fat diet is a risk factor for the development of inflammatory bowel disease (IBD) in humans. Deoxycholate (DOC) is increased in the colonic contents in response to a high-fat diet. Thus, an elevated level of DOC in the colonic lumen may play a role in the natural course of development of IBD. Methods: Wild-type B6.129 mice were fed an AIN-93G diet, either supplemented with 0.2% DOC or unsupplemented and sacrificed at 1 week, 1 month, 3 months, 4 months, and 8 months. Colon samples were assessed by histopathological, immunohistochemical, and cDNA microarray analyses. Results: Mice fed the DOC-supplemented diet developed focal areas of colonic inflammation associated with increases in angiogenesis, nitrosative stress, DNA/RNA damage, and proliferation. Genes that play a central role in inflammation and angiogenesis and other related processes such as epithelial barrier function, oxidative stress, apoptosis, cell proliferation/cell cycle/DNA repair, membrane transport, and the ubiquitin-proteasome pathway showed altered expression in the DOC-fed mice compared with the control mice. Changes in expression of individual genes (increases or reductions) correlated over time. These changes were greatest 1 month after the start of DOC feeding. Conclusions: The results suggest that exposure of the colonic mucosa to DOC may be a key etiologic factor in IBD. The DOC-fed mouse model may reflect the natural course of development of colitis/IBD in humans, and thus may be useful for determining new preventive strategies and lifestyle changes in affected individuals.

Original languageEnglish (US)
Pages (from-to)278-293
Number of pages16
JournalInflammatory Bowel Diseases
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2006

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Keywords

  • Angiogenesis
  • Bile acids
  • Colitis
  • Deoxycholate
  • IBD
  • Inflammation

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Bernstein, H., Holubec, H., Bernstein, C., Ignatenko, N., Gerner, E., Dvorak, K., ... Payne, C. M. (2006). Unique dietary-related mouse model of colitis. Inflammatory Bowel Diseases, 12(4), 278-293. https://doi.org/10.1097/01.MIB.0000209789.14114.63