The microbial basis of inflammatory bowel diseases

Abstract

Inflammatory bowel diseases (IBD) are chronic, progressive diseases characterized by aberrant immune responses to environmental and gut microbial triggers in genetically susceptible hosts. Clinical, genetic, and experimental data support the role of gut microbes in causing and sustaining these diseases. Our understanding of IBD has changed dramatically as the result of advances in cultivation-independent approaches and computational platforms for the analysis of large data sets. However, investigations relevant to clinical observations and the natural history of the diseases will be essential for the development of microbial, genetic, and biological metrics that may be used to individualize assessment of risk and improve clinical outcomes in IBD.

Figure 2. IBD are chronic, progressive diseases.

The composition and function of the gut microbiota likely change through the course (natural history) of IBD, reflecting transitions in host-microbe relationships that arise from disease-intrinsic and confounding factors. Microbial factors that trigger the onset of disease may be quite different from those that sustain the inflammatory process or result from the consequences of long-term complications and interventions. The interpretation of gut microbial data in the absence of this contextual information can be limited and potentially misleading. The pie charts in this figure illustrate the concept of general shifts in microbial composition and/or function over time and are not meant to indicate any quantifiable information.

Figure 1. IBD are caused by a confluence of factors that perturb the balance between the environment, gut microbes, and host.

IBD are believed to arise from a “perfect storm” that involves the confluence of environmental and genetic factors tipping the balance between host immune and gut microbial factors and thus triggering disease in genetically susceptible individuals. IBD are maintained by pathophysiological host processes and events that feed forward to promote a dysbiotic microbiota that can in turn worsen inflammation and create a vicious loop.