Restoring the gut microbiome for the treatment of inflammatory bowel diseases

Abstract

Fecal microbiota transplantation (FMT) is considered to be a highly successful therapy for recurrent and refractory Clostridium difficile infection (CDI) based on recent clinical trials. The pathogenesis of inflammatory bowel diseases (IBD) is thought to be due in part to perturbations in the gut microflora that disrupt homeostasis. FMT restores essential components of the microflora which could reverse the inflammatory processes observed in IBD. Case reports and series for the treatment of IBD by FMT have shown promise with regards to treatment success and safety despite the limitations of the reporting. Future studies will determine the optimal delivery and preparation of stool as well as the conditions under which the recipient will derive maximal benefit. The long term consequences of FMT with regards to infection, cancer, auto-immune, and metabolic diseases are not known and will require continued regulation and study. Despite these limitations, FMT may be beneficial for the treatment of ulcerative colitis and Crohn’s disease, particularly those with concurrent CDI or with pouchitis.

Keywords: Crohn’s; Ulcerative colitis; Microbiota; Fecal transplantation; Dysbiosis; Pouchitis; Clostridium difficile; Probiotic

Core tip: Advances into the understanding of the pathogenesis of inflammatory bowel diseases (IBD) have highlighted the importance of a dysbiosis in the intestinal microbiome. A perturbed microbiota with loss of colonization resistance is a main driver of Clostridium difficile infection and exciting new data exists that microbial restoration through the use of fecal microbiota transplantation (FMT) is highly successful. Therefore, it is logical to conclude that FMT will have therapeutic efficacy in IBD. Preliminary studies that have evaluated FMT for IBD are reviewed with an emphasis on subpopulations that may benefit the most. The limitations and unknowns for this novel therapy are also discussed.