Immunological mechanisms underpinning faecal microbiota transplantation for the treatment of inflammatory bowel disease

Abstract

Summary Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease that results from a dysregulated immune response against specific environmental triggers in a genetically predisposed individual. Increasing evidence has indicated a causal role for changes in gut microbiota (dysbiosis) contributing to this immune‐mediated intestinal inflammation. These mechanisms involve dysregulation of multiple facets of the host immune pathways that are potentially reversible. Faecal microbiota transplantation (FMT) is the transfer of processed stool from a healthy donor into an individual with an illness. FMT has shown promising results in both animal model experiments and clinical studies in IBD in the resolution of intestinal inflammation. The underlying mechanisms, however, are unclear. Insights from these studies have shown interactions between modulation of dysbiosis via changes in abundances of specific members of the gut microbial community and changes in host immunological pathways. Unravelling these causal relationships has promising potential for a translational therapy role to develop targeted microbial therapies and understand the mechanisms that underpin IBD aetiopathogenesis. In this review, we discuss current evidence for the contribution of gut microbiota in the disruption of intestinal immune homeostasis and immunoregulatory mechanisms that are associated with the resolution of inflammation through FMT in IBD.

Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies

“…In addition, faecal microbiota transplantation (FMT), the transfer of stool from a healthy donor to a UC patient is emerging as a promising approach to alleviating UC severity. FMT has been shown to result in increased secretory IgA and mucin as well as anti-microbial peptide production, affecting pathogen invasion by antigen/pathogendependent and -independent targeting [65]. In the case of UC, a few randomised controlled trials are currently underway, with one recent study showing that some UC patients could achieve remission following continuous FMT thanks to the observed greater microbial diversity and enrichment of Eubacterium hallii and Roseburia inulivorans in faecal and colon samples [66].…”

Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease

“…The human gut microbiota (hGM) is comprised of bacteria, viruses, fungi, protozoa and archaea, which collectively, may have functionally distinct proinflammatory or anti-inflammatory roles, as described in animal models. 1 Alterations in the compositional balance of microbial communities, also termed "dysbiosis," has been hypothesized to play a central role in human diseases. However, the causal connection between the gut microbiome and the pathogenesis of human diseases remains uncertain, as pathogenicity studies with animal models have been deemed implausibly biased, "exaggerating causality."…”

Interactions of the microbiota with the mucosal immune system

“…The effectiveness of this treatment, most notably in recurrent Clostridium difficile infection, has been extraordinary and has provided a real impetus to the development of microbiotabased therapies in IBD and other inflammatory disorders. Quraishi et al 13 stress a pressing need to understand the mechanisms by which FMT confers its beneficial effects. Indeed, characterizing the molecular and cellular interactions by which FMT modulates the host immune system may lead to safer and more effective microbiota-based therapies.…”