Unique dietary-related mouse model of colitis.
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.
Bernstein
Harris
H
Department of Cell Biology and Anatomy, College of Medicine, Tucson, AZ 85724, USA. bernstein3@earthlink.net
Holubec
Hana
H
Bernstein
Carol
C
Ignatenko
Natalia
N
Gerner
Eugene
E
Dvorak
Katerina
K
Besselsen
David
D
Ramsey
Lois
L
Dall'Agnol
Monique
M
Blohm-Mangone
Karen Ann
KA
Padilla-Torres
Jose
J
Cui
Haiyan
H
Garewal
Harinder
H
Payne
Claire Margaret
CM
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D003092:Colitis / Q000209:etiology* / Q000473:pathology; D004247:DNA / Q000235:genetics; D004041:Dietary Fats / Q000633:toxicity*; D004195:Disease Models, Animal; D018450:Disease Progression; D005500:Follow-Up Studies; D015870:Gene Expression; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics
D004041:Dietary Fats; D018809:Proliferating Cell Nuclear Antigen; D004247:DNA