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Infection and Immunity, February 2005, p. 912-920, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.912-920.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Probiotic Lactobacillus spp. Diminish Helicobacter hepaticus-Induced Inflammatory Bowel Disease in Interleukin-10-Deficient Mice

Jeremy A. Peña,1,2,3 Arlin B. Rogers,4 Zhongming Ge,4 Vivian Ng,4 Sandra Y. Li,2,3 James G. Fox,4 and James Versalovic1,2,3*

Departments of Molecular Virology & Microbiology,1 Pathology, Baylor College of Medicine,2 Department of Pathology, Texas Children's Hospital, Houston, Texas,3 Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts4

Received 20 July 2004/ Returned for modification 24 September 2004/ Accepted 18 October 2004

Clinical and experimental evidence has demonstrated the potential role of probiotics in the prevention or treatment of inflammatory bowel disease. Probiotic clones with direct immunomodulatory activity may have anti-inflammatory effects in the intestine. We investigated the roles of tumor necrosis factor alpha (TNF-{alpha})-inhibitory Lactobacillus clones with a pathogen-induced murine colitis model. Murine-derived probiotic lactobacilli were selected in vitro for their ability to inhibit TNF-{alpha} secretion by Helicobacter hepaticus-stimulated macrophages. Interleukin-10 (IL-10)-deficient mice were treated with probiotic Lactobacillus reuteri in combination with Lactobacillus paracasei and then challenged with H. hepaticus. Ten weeks postinoculation, the severity of typhlocolitis was assessed by histologic examination of the cecocolic region. Intestinal proinflammatory cytokine responses were evaluated by real-time quantitative reverse transcriptase PCR and immunoassays, and the quantities of intestinal H. hepaticus were evaluated by real-time PCR. Intestinal colonization by TNF-{alpha}-inhibitory lactobacilli reduced intestinal inflammation in H. hepaticus-challenged IL-10-deficient mice despite similar quantities of H. hepaticus in cocolonized animals. Proinflammatory colonic cytokine (TNF-{alpha} and IL-12) levels were lowered in Lactobacillus-treated animals. In this H. hepaticus-challenged IL-10-deficient murine colitis model, lactobacilli demonstrated probiotic effects by direct modulation of mucosal inflammatory responses.

* Corresponding author. Mailing address: Texas Children's Hospital, Department of Pathology, 6621 Fannin St., MC 1-2261, Houston, TX 77030. Phone: (832) 824-2213. Fax: (832) 825-1032. E-mail: jxversal{at}texaschildrenshospital.org.

Editor: F. C. Fang

Infection and Immunity, February 2005, p. 912-920, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.912-920.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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