Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Clostridium difficile infection (CDI) is the most important cause of hospital-acquired diarrhea. In the majority of patients, CDI resolves after initial antimicrobial treatment. However, recurrent CDI can occur in as many as 35 percent of these patients. Recurrences are associated with the persistence of a compromised intestinal flora. Fecal transplantation, which consists of infusing feces from a healthy donor into a patient's gastrointestinal tract, has recently been described as an effective alternative for the treatment of recurrent CDI. The procedure is thought to restore a normal, functional intestinal flora. However, it has not been widely implemented. We propose to conduct a randomized controlled trial (RCT) of fecal transplantation in patients with relapsing CDI. The objectives of this study are to (i) test the effectiveness of fecal transplantation in relapsing CDI patients, and (ii) describe changes in the composition of the intestinal flora following transplantation. The effectiveness of fecal transplantation (n=55 patients) will be compared to the standard antimicrobial therapy for recurrent CDI (n=55 patients). Stool specimens will be collected from each patient at multiple time-points before and after transplantation. These specimens will be subjected to 16S ribosomal RNA-based sequencing in order to examine the composition of the patients' intestinal flora. This RCT will rigorously test, for the first time, the effectiveness and safety of a defined fecal transplantation procedure for the treatment of recurrent CDI. The implementation of a proven protocol will dramatically improve the quality of life of the patients and will result in significant medical cost savings. The study will also provide important new insight into the mechanism of normal intestinal flora restoration and CDI resolution. Although speculative, diseases such as irritable bowel syndrome and obesity may be amenable to similar therapeutic approaches.