Grant: Project Grant

Clostridioides difficile infection (CDI), the most common bowel infection in the hospital setting, is usually triggered by antibiotics. The treatment for CDI is with another antibiotic called vancomycin. After treatment, the chance of CDI coming back is about 20% after the initial episode, increasing to at least 60% after the 3rd episode. Fecal microbiota transplantation (FMT), or stool transplant, is the most effective therapy for recurrent CDI (RCDI). The success rate is 80-90%. However, we don't know how it works. Recently there were 2 cases of mutli-drug resistant organism (MDRO) transmitted through FMT, resulting in one death. Both patients were immunosuppressed and their donor was not tested for MDRO. Furthermore, we do not know if there are long-term effects. For example, studies in mice have shown that obesity can be transferred with FMT, thus raising the possibility that other conditions such as autoimmune diseases and cancer could potentially be transferred with FMT. Therefore, safer and targeted therapy is needed, but we need to understand how FMT works first. The assumption is that transferring healthy gut bacteria from a donor to a patient corrects the disrupted gut bacterial community, but there may be more to this. A recent study showed despite removing live bacteria from donor stool, 5 RCDI patients were still successfully treated. This brings into question whether components in the stool other than live bacteria may be crucial. We believe that live bacteria may not be necessary for FMT to work. In this proposal, we will compare two forms of FMT: one with live bacteria and one without. Both formulations will be freeze-dried and put into pills. By removing live bacteria from the equation, this study will conclusively show whether other components within stool are enough to reshape the bacterial community in the gut. The results will lay foundation for future effort in developing more targeted RCDI treatment.