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Unique dietary-related mouse model of colitis.

Harris Bernstein1, Hana Holubec, Carol Bernstein

  • 1Department of Cell Biology and Anatomy, College of Medicine, Tucson, AZ 85724, USA. bernstein3@earthlink.net

Inflammatory Bowel Diseases
|April 25, 2006
PubMed
Summary

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High-fat diets increase deoxycholate (DOC), a bile acid linked to inflammatory bowel disease (IBD) development. This study shows DOC exposure in mice causes colonic inflammation, suggesting it

Area of Science:

  • Gastroenterology
  • Immunology
  • Molecular Biology

Background:

  • High-fat diets are a known risk factor for inflammatory bowel disease (IBD).
  • Deoxycholate (DOC), a bile acid, increases in the colon with high-fat diets.
  • Elevated colonic DOC may contribute to IBD pathogenesis.

Purpose of the Study:

  • To investigate the role of deoxycholate (DOC) in the development of colonic inflammation.
  • To establish a mouse model for studying IBD development induced by DOC.

Main Methods:

  • Wild-type mice were fed a standard diet or one supplemented with 0.2% DOC.
  • Colon tissues were collected at multiple time points (1 week to 8 months).
  • Analyses included histopathology, immunohistochemistry, and cDNA microarray.

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Main Results:

  • DOC-fed mice developed focal colonic inflammation, increased angiogenesis, nitrosative stress, DNA/RNA damage, and proliferation.
  • Gene expression changes related to inflammation, angiogenesis, barrier function, and cell cycle were observed.
  • These molecular and pathological changes were most pronounced at 1 month of DOC feeding.

Conclusions:

  • Colonic mucosal exposure to DOC may be a significant etiological factor in IBD.
  • The DOC-induced mouse model may mimic human colitis/IBD development.
  • This model can aid in developing preventive strategies and lifestyle interventions for IBD.