The high recurrence rate of CDI following standard antibiotic therapy is a global concern. Toxoid vaccines [22,23] and intestinal transplantation of nontoxigenic C. difficile [24,25] have previously been reported as possible alternatives to standard antibiotic therapy; however, toxoids prepared by formaldehyde treatment can revert to their original active state, and transplanted nontoxigenic strains are capable of acquiring toxin genes from other intestinal pathogens including toxigenic C. difficile via lateral gene transfer. Furthermore, as C. difficile toxins play no role in colonization [26], toxoids are unable to inhibit colonization. In this study, we considered the potential of vaccination with C. difficile membrane as a more effective countermeasure for CDI.