Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease

Abstract

The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models.

Keywords: Inflammatory bowel disease, Intestinal microbiota, Probiotics, Fecal microbiota transplantation, Synthetic microbiota transplantation

Core tip: Several lines of evidence strongly support the link between intestinal microbiota and inflammatory bowel disease (IBD). This review discusses the potential microbial pathogens, disturbance of intestinal microbiota, and immune interactions between host and microbes in IBD. Furthermore, alternative IBD treatment approaches aimed at restoring the disturbed intestinal microbiota have become a major interest in recent years. This article also reviews the present literature concerning the clinical use of probiotics, especially fecal microbiota transplantation and its barriers, and future directions in the management of IBD.