Mechanisms of action and applications of probiotics for the treatment of Clostridium difficile infection

Clostridium difficile is a spore-forming Gram-positive anaerobic bacillus, and is the leading cause of nosocomial diarrhea and colitis in the industrialized world. The incidence and mortality rates of C. difficile infection (CDI) have increased dramatically in the past decade. CDI is difficult to treat as antibiotic options are limited. Moreover, 15-35% of patients infected with C. difficile relapse following antibiotic treatment, which limits the ability of the colonic flora to inhibit C. difficile colonization. In an effort to improve outcomes and reduce recurrences of CDI, interest has been renewed in the development of nonantibiotic and adjunct approaches to therapy. Among these, probiotics have been investigated for primary and secondary prophylaxis against CDI, with varying success. This review discusses the mechanisms by which probiotics interact with C. difficile and its toxins, evaluates experimental models and clinical trials for probiotic use in the prevention or treatment of CDI and provides a framework for future research directions.