Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases

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http://www3.interscience.wiley.com/journal/120756832/abstract?CRETRY=1 & SRETRY=0

Review Article

Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases

Vanderpool, MD 1, Fang Yan, MD, PhD 1, D. Brent Polk, MD 1 2 *

1Department of Pediatrics, Division of Gastroenterology, Hepatology & Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee2Department of Cell & Developmental Biology, Division of Gastroenterology, Hepatology & Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee

email: D. Brent Polk (d-brent.polk@...)

*Correspondence to D. Brent Polk, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 2215 Garland Ave., MRB IV, Room 1025, Nashville, TN 37232-0696

Keywords

probiotics • mechanism • intestinal epithelial cell • immune response • signaling pathway

Abstract

Probiotics are defined as nonpathogenic living microorganisms, including some commensal bacterial flora, which have beneficial effects on host health and disease prevention and/or treatment. Clinical trials have shown beneficial effects of probiotics on several human diseases, such as inflammatory bowel diseases (IBDs), which are among the most-studied diseases testing probiotics as a potential therapy. However, a significant question regarding clinical use of probiotics is the mechanism underlying the wide range of actions. Studies discussed in this review suggest 3 distinct cellular and molecular mechanisms for probiotic regulation in IBD therapy: 1) Probiotics block pathogenic bacterial effects by producing bactericidal substances and competing with pathogens and toxins for adherence to the intestinal epithelium; 2) Probiotics regulate immune responses by enhancing the innate immunity and modulating pathogen-induced inflammation via toll-like receptor-regulated signaling pathways; and 3) Probiotics regulate intestinal epithelial homeostasis by promoting intestinal epithelial cell survival, enhancing barrier function, and stimulating protective responses. Probiotics modulate host cell signaling pathways, including Akt, mitogen-activated protein kinases, and nuclear factor-B to mediate these intestinal epithelial functions. It is hoped that developing a mechanistic understanding of probiotic action will provide the rationale to support the development of new hypothesis-driven studies to define the clinical efficacy in preventive, adjunctive, or alternative treatments for IBD.

(Inflamm Bowel Dis 2008)

Received: 29 April 2008; Accepted: 8 May 2008

Digital Object Identifier (DOI)10.1002/ibd.20525