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Published ahead of print on January 4, 2007, doi:10.1164/rccm.200606-821OC
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American Journal of Respiratory and Critical Care Medicine Vol 175. pp. 561-569, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200606-821OC


Original Article

Oral Treatment with Live Lactobacillus reuteri Inhibits the Allergic Airway Response in Mice

Paul Forsythe1, Mark D. Inman2 and John Bienenstock1

1 The Brain–Body Institute and Department of Pathology and Molecular Medicine and 2 Firestone Institute for Respiratory Health, McMaster University, and St. Joseph's Healthcare, Hamilton, Ontario, Canada

Correspondence and requests for reprints should be addressed to John Bienenstock, M.D., Departments of Pathology and Molecular Medicine, McMaster University, Brain–Body Institute, St. Joseph's Healthcare, 50 Charlton Avenue East, T3304 Hamilton, ON, L8N 4A6 Canada. E-mail: bienens{at}mcmaster.ca

Rationale: Clinical trials have demonstrated that probiotics may be effective in the treatment and prevention of atopic disease in children but there have been few reports of therapeutic effects of oral probiotics outside the gastrointestinal tract.

Objectives: We investigated the effect of two probiotic organisms on the response to antigen challenge in a mouse model of allergic airway inflammation.

Methods: We used an ovalbumin-sensitized asthma model in BALB/c and Toll-like receptor 9–deficient mice. Animals were treated with probiotic organisms via gavaging needle before antigen challenge. After antigen challenge, airway responsiveness to methacholine, influx of inflammatory cells to the lung, and cytokine levels in bronchoalveolar lavage fluid were assessed.

Results: Oral treatment with live Lactobacillus reuteri but not Lactobacillus salivarius significantly attenuated the influx of eosinophils to the airway lumen and parenchyma and reduced the levels of tumor necrosis factor, monocyte chemoattractant protein-1, IL-5, and IL-13 in bronchoalveolar lavage fluid of antigen-challenged animals, but there was no change in eotaxin or IL-10. L. reuteri but not L. salivarius also decreased allergen-induced airway hyperresponsiveness. These responses were dependent on Toll-like receptor 9 and were associated with increased activity of indoleamine 2,3-dioxygenase. Killed organisms did not mimic the ability of the live L. reuteri to attenuate inflammation or airway hyperresponsiveness.

Conclusion: Oral treatment with live L. reuteri can attenuate major characteristics of an asthmatic response in a mouse model of allergic airway inflammation. These results suggest that oral treatment with specific live probiotic strains may have therapeutic potential in the treatment of allergic airway disease.

Key Words: airway inflammation • bronchial hyperresponsiveness • probiotics • Toll-like receptor 9 • mouse model


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Despite indications that probiotics can modulate immune responses in the lung, there have been no reports of the effects of oral treatment with a probiotic on major characteristics of asthma, including airway inflammation and hyperresponsiveness.

What This Study Adds to the Field
Oral treatment with a probiotic organism can attenuate major characteristics of an asthmatic response, including airway eosinophilia, local cytokine responses, and hyperresponsiveness.

 



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