Gastroenterology

Gastroenterology

Volume 121, Issue 3, September 2001, Pages 580-591
Gastroenterology

Alimentary Tract
Probiotic bacteria enhance murine and human intestinal epithelial barrier function,☆☆

https://doi.org/10.1053/gast.2001.27224Get rights and content

Abstract

Background & Aims: The probiotic compound, VSL#3, is efficacious as maintenance therapy in pouchitis and ulcerative colitis. The aim of this study was to determine the efficacy of VSL#3 as a primary therapy in the treatment of colitis in the interleukin (IL)-10 gene-deficient mouse. Mechanisms of action of VSL#3 were investigated in T84 monolayers. Methods: IL-10 gene-deficient and control mice received 2.8 × 108 colony-forming units per day of VSL#3 for 4 weeks. Colons were removed and analyzed for cytokine production, epithelial barrier function, and inflammation. VSL#3 or conditioned media was applied directly to T84 monolayers. Results: Treatment of IL-10 gene-deficient mice with VSL#3 resulted in normalization of colonic physiologic function and barrier integrity in conjunction with a reduction in mucosal secretion of tumor necrosis factor α and interferon γ and an improvement in histologic disease. In vitro studies showed that epithelial barrier function and resistance to Salmonella invasion could be enhanced by exposure to a proteinaceous soluble factor secreted by the bacteria found in the VSL#3 compound. Conclusions: Oral administration of VSL#3 was effective as primary therapy in IL-10 gene-deficient mice, and had a direct effect on epithelial barrier function.

GASTROENTEROLOGY 2001;121:580-591

Section snippets

Animals

Homozygous IL-10 gene-deficient mice, generated on a 129 Sv/Ev background, and normal 129 Sv/Ev controls were housed behind a barrier under specific pathogen-free conditions. All provisions for the facility were sterilized using an autoclave. Nonautoclavable supplies were sprayed with disinfectant and introduced into the facility through a high-efficiency particulate air (HEPA)-filtered air-lock. The facility's air was HEPA-filtered. The mice were housed in micro isolator cages covered with

Colonic bacteria

To confirm that the oral administration of the VSL#3 compound resulted in viable organisms reaching the colon, total and adherent levels of Lactobacillus spp. and Bifidobacteria spp. were measured in control and IL-10 gene-deficient mice after 4 weeks of treatment. There was no difference between controls and IL-10 gene-deficient mice in the total amount of Lactobacillus and Bifidobacteria (Figure 1A).

. Colonic mucosal (A) total and (B) adherent levels of Lactobacillus spp. and Bifidobacterium

Discussion

In the present study, we have shown that treatment of IL-10 gene-deficient mice with the probiotic compound, VSL#3, results in a normalization of colonic physiologic function and barrier integrity in conjunction with a reduction in mucosal levels of proinflammatory cytokines and a significant improvement in histologic disease. Furthermore, in vitro studies show that epithelial barrier function can be modulated by exposure to proteinaceous soluble factor(s) secreted by the probiotic bacteria

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    Address requests for reprints to: Karen L. Madsen, Ph.D., University of Alberta, 536 Newton Building, Edmonton, Alberta, Canada T6G 2C2. e-mail: [email protected]; fax: (780) 407-3744.

    ☆☆

    Supported by grants from Alberta Heritage Foundation for Medical Research, Crohn's and Colitis Foundation of Canada, and Gastrointestinal Liver Disease Research Group.

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