Elucidating the factors that determine success in fecal transplant therapy for C. difficile infection
Patient Safety and Quality of Care
Through these studies we will gain a better understanding of the mechanisms underlying successful fecal microbial therapy for recurrent CDI, which will help us to further refine microbial therapy for C. difficile.
Clostridium difficile infection (CDI) is a leading cause of nosocomial diarrhea and a major cause of morbidity and mortality in hospitalized patients. Antibiotic use causes decreased diversity of resident gut microbiota and loss of colonization resistance against C. difficile. There is a direct link between recurrent CDI and intestinal dysbiosis i.e. there is an inability of certain individuals to “re-establish” their normal protective bacterial flora. In these cases, fecal microbiota transplantation (FMT) has been effectively used to treat nonresponsive recurrent CDI where patients cannot recover their indigenous gut microbiota following antibiotic exposure. Aim: to gain a better understanding of the mechanisms underlying successful fecal microbial therapy for recurrent CDI. Hypothesis: FMT treatment failures may be dependent on donor stool composition, and more diverse fecal microbial ecosystems may be more robust than others. Intestinal bacterial communities were grown to equilibrium in a bioreactor (models the anaerobic conditions of the distal human gut). A donor FMT community was compared to a “synthetic” stool preparation (defined community). Using RISA (Ribosomal Intergenic Spacer Analysis), a molecular fingerprinting method of microbial community structure analysis, measures of ecosystem community dynamics, Shannon diversity index, and community richness, were determined both in the presence and absence of ecosystem perturbation (antibiotics). A full microbial consortium (FMT), was better able to withstand antibiotic perturbation than the smaller, defined community. However, since some treatment failures occurred with this FMT, and conversely, the defined community was successful at curing recurrent CDI, we conclude that diversity plays a contributing role but is not the sole determinant in success of FMT.