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

Core tip: In the last decade there have been enormous strides in our understanding of the role of gut microbiota in the aetiopathogenesis of inflammatory bowel disease (IBD). Newer molecular and genetic diagnostic tools have elucidated distinct changes in the gut microbiota in IBD patients and clarified the deficiencies of innate immunity. A link between environmental factors like diet, host immunity and the gut microbiota has been established. This review aims to enumerate these diverse strands of converging research in the last decade to outline the exciting prospects of possible personalized therapeutic interventions for patients with IBD in the coming years.