Inflammatory Bowel Diseases (IBD) and the Microbiome-Searching the Crime Scene for Clues

Abstract

Inflammatory bowel diseases (IBD) develop via convergence of environmental, microbial, immunological, and genetic factors. Alterations in the gut microbiota have been associated with development and progression of IBD, but it is not clear which populations of microbes are involved or how they might contribute to IBD. We review the genetic and environmental factors affecting the gut microbiota, the roles of gut microbes and their bioproducts in the development and clinical course of IBD, and strategies by which microbiome-based therapies can be used to prevent, manage, and eventually cure IBD. We discuss research findings that help bridge the gap between the basic sciences and clinical application.

Keywords: Colitis; Dysbiosis; Host-Microbe Interactions; Intestinal Microbiome; Mucosal Inflammation.

Figure 1.. Factors influencing dysbiotic and chronic inflammatory state in IBD.

In healthy individuals, commensal bacteria provide functions that benefit the host. (left) Certain bacteria produce short-chain fatty acids (SCFAs) such as butyrate to regulate intestinal homeostasis. Antimicrobial peptides produced by Paneth cells and the intact mucus layer prevent bacterial invasion of the epithelial layer. SCFAs are an energy source for the epithelial cells and help maintain a functional barrier. SCFAs also provide anti-inflammatory properties by facilitating differentiation of regulatory T-cells (Treg) and effector T-cells (Teff). However, in IBD patients, perturbations due to genetic and/or environmental factors lead to dysbiosis of the gut microbiota. (right) IBD patients display a reduction of commensal bacteria, including SCFA-producing bacteria. This leads to decrease in SCFAs and their beneficial effects including the ability to modulate Treg and Teff differentiation. The imbalance of Treg and Teff cells leads to increased production of proinflammatory cytokines. Due to the perturbations, the mucosal layer is damaged, leading to a dysfunctional barrier. This allows for bacterial penetration, triggering an inflammatory cascade against the invading bacteria. Furthermore, pathobionts, commensal bacteria that can display pathogenic properties given the right opportunity, emerge and expand in the inflammatory conditions. This continues to promote inflammatory conditions, allowing for the adapted pathobionts to survive and further limiting commensal growth. The loss of commensals, emergence of pathobionts, and the imbalance of immune regulation leads to a chronic inflammatory state.