Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years?

Abstract

Our understanding of the microbial involvement in inflammatory bowel disease (IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn's disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or "dysbiosis" is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity (including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.

Keywords: Crohn’s disease; Faecal transplant; Gut microbiota; Inflammatory bowel disease; Innate immune response; Prebiotics; Probiotics; Ulcerative colitis.

Figure 1

The Venn diagram depicts the overlapping role of the gut microbiome, host and environmental factors in the aetiopathogenesis of inflammatory bowel disease. Dysbiotic changes in the gut microbiome may be influenced by diet and other environmental factors and predispose to inflammatory bowel disease (IBD). A small proportion of IBD patients have demonstrable genetic susceptibility factors. NOD2: Nucleotide-binding oligomerization domain-containing protein 2; ATG16L1: Autophagy related protein 16-like 1; IL-23R: Interleukin 23 receptor.