Probiotics for the treatment of Clostridium difficile associated disease

Abstract

The purpose of this review paper is to update the current and potential future role of probiotics for Clostridium difficile-associated disease (CDAD). Included in this review, is an update on the testing of newer probiotics (e.g., Bacillus coagulans GBI-30, 6086) in animal models of CDAD. There is a focus on the modulation of signal transduction pathways (i.e., transcription factors like cAMP response element-binding, activator protein 1, and nuclear factor kappa B), as well as the inhibition of certain kinases (e.g., p38 mitogen activated protein kinases) by probiotics. Inhibition of signal transduction by probiotics, such as Saccharomyces boulardii, result in multiple effects on intestinal fluid secretion, neutrophil influx into the colon, inflammation, and colonocyte apoptosis that may positively impact CDAD. Recent clinical approaches with probiotics, for the prevention of primary and recurrent CDAD, are also summarized in this review paper. Future directions for the treatment of CDAD by probiotics are also mentioned in this review. In particular, the use of multi-strain probiotic formulations such as Ecologic^® AAD and VSL #3^® may represent a rationale pharmacological approach, particularly as adjunctive therapies for CDAD. Understanding the mechanistic basis of CDAD, and how probiotics interfere at ceratin steps in the pathogenic process, may also present the opportunity to design other multi-strain probiotics that could have a future impact on CDAD.

Keywords: Clostridium difficile, Colitis, Probiotics, Mechanisms of action, Immune modulation, Transcription factors, Saccharomyces boulardi, VSL#3

Core tip: Certain probiotics can inhibit signal transduction pathways (i.e., transcription factors like cAMP response element-binding, activator protein 1, and nuclear factor kappa B), as well as attenuate the activation of ceratin certain kinases (e.g., p38 mitogen activated protein kinases). Inhibition of these Intracellular signaling pathways by probiotics results in effects on intestinal fluid secretion, neutrophil influx into the colon, inflammation and colonocyte apoptosis that may positively impact Clostridium difficile-associated disease (CDAD). Understanding the mechanistic basis of CDAD, and how probiotics interfere at certain steps in the pathogenic process, may allow the development of novel probiotics that could have a future pharmacological impact on CDAD.