The microbiome in inflammatory bowel disease: current status and the future ahead

Abstract

Studies of the roles of microbial communities in the development of inflammatory bowel disease (IBD) have reached an important milestone. A decade of genome-wide association studies and other genetic analyses have linked IBD with loci that implicate an aberrant immune response to the intestinal microbiota. More recently, profiling studies of the intestinal microbiome have associated the pathogenesis of IBD with characteristic shifts in the composition of the intestinal microbiota, reinforcing the view that IBD results from altered interactions between intestinal microbes and the mucosal immune system. Enhanced technologies can increase our understanding of the interactions between the host and its resident microbiota and their respective roles in IBD from both a large-scale pathway view and at the metabolic level. We review important microbiome studies of patients with IBD and describe what we have learned about the mechanisms of intestinal microbiota dysfunction. We describe the recent progress in microbiome research from exploratory 16S-based studies, reporting associations of specific organisms with a disease, to more recent studies that have taken a more nuanced view, addressing the function of the microbiota by metagenomic and metabolomic methods. Finally, we propose study designs and methodologies for future investigations of the microbiome in patients with inflammatory gut and autoimmune diseases in general.

Keywords: Crohn's Disease; Metagenomics; Microbiota; Ulcerative Colitis.

Conflict of interest statement

Conflicts of interest: The authors report no conflict of interest.

Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Factors affecting the stability and complexity of the gut microbiome in health and disease

Key characteristics of the microbiome, including stability, resilience, and complexity, are influenced over time from infancy through adulthood and in old age. In the healthy gut, these characteristics contribute to important physiological processes such as protection against pathogens, training of the immune system, and digestion of food to supply energy and nutrients including vitamins and SCFAs. Many factors are indicated to impact the microbiome throughout microbiome development and even established assembly, including genetics, diet, medication, among others (marked in the grey boxes at the top of the figure). Some of these factors can introduce perturbations affecting the complexity and stability of the microbiome, potentially introducing microbial dysbiosis. Features of an imbalanced microbiome include, for example, an increase in Gram-negative bacteria linked to an environment of oxidative stress and inflammation, and metabolite production.

Figure 2. A multifaceted approach to study the role of the microbiome in IBD

Future microbiome studies in the context of disease will shift towards multi-omics approaches in order to study host-microbe relations more comprehensively. Optimized sample collection, detailed clinical annotation, and sample processing will be key to expand data generation far beyond the typical marker gene and shotgun sequencing approaches. A number of assays on the host side (red) and microbial end (blue) will gain increasing attention going forward.