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Colitis and colon cancer in WASP-deficient mice require helicobacter species.

Abstract：

BACKGROUND:Wiskott-Aldrich syndrome protein-deficient patients and mice are immunodeficient and can develop inflammatory bowel disease. The intestinal microbiome is critical to the development of colitis in most animal models, in which Helicobacter spp. have been implicated in disease pathogenesis. We sought to determine the role of Helicobacter spp. in colitis development in Wiskott-Aldrich syndrome protein-deficient (WKO) mice. METHODS:Feces from WKO mice raised under specific pathogen-free conditions were evaluated for the presence of Helicobacter spp., after which a subset of mice were rederived in Helicobacter spp.-free conditions. Helicobacter spp.-free WKO animals were subsequently infected with Helicobacter bilis. RESULTS:Helicobacter spp. were detected in feces from WKO mice. After rederivation in Helicobacter spp.-free conditions, WKO mice did not develop spontaneous colitis but were susceptible to radiation-induced colitis. Moreover, a T-cell transfer model of colitis dependent on Wiskott-Aldrich syndrome protein-deficient innate immune cells also required Helicobacter spp. colonization. Helicobacter bilis infection of rederived WKO mice led to typhlitis and colitis. Most notably, several H. bilis-infected animals developed dysplasia with 10% demonstrating colon carcinoma, which was not observed in uninfected controls. CONCLUSIONS:Spontaneous and T-cell transfer, but not radiation-induced, colitis in WKO mice is dependent on the presence of Helicobacter spp. Furthermore, H. bilis infection is sufficient to induce typhlocolitis and colon cancer in Helicobacter spp.-free WKO mice. This animal model of a human immunodeficiency with chronic colitis and increased risk of colon cancer parallels what is seen in human colitis and implicates specific microbial constituents in promoting immune dysregulation in the intestinal mucosa.

journal_name

Inflamm Bowel Dis

journal_title

Inflammatory bowel diseases

authors

Nguyen DD,Muthupalani S,Goettel JA,Eston MA,Mobley M,Taylor NS,McCabe A,Marin R,Snapper SB,Fox JG

doi

10.1097/MIB.0b013e318295fd8f

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

2041-50

issue

eissn

1078-0998

issn

1536-4844

journal_volume

pub_type

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Colitis and colon cancer in WASP-deficient mice require helicobacter species.