Dysbiosis in Inflammatory Bowel Disease: Pathogenic Role and Potential Therapeutic Targets

Abstract

Microbe-host communication is essential to maintain vital functions of a healthy host, and its disruption has been associated with several diseases, including Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD). Although individual members of the intestinal microbiota have been associated with experimental IBD, identifying microorganisms that affect disease susceptibility and phenotypes in humans remains a considerable challenge. Currently, the lack of a definition between what is healthy and what is a dysbiotic gut microbiome limits research. Nevertheless, although clear proof-of-concept of causality is still lacking, there is an increasingly evident need to understand the microbial basis of IBD at the microbial strain, genomic, epigenomic, and functional levels and in specific clinical contexts. Recent information on the role of diet and novel environmental risk factors affecting the gut microbiome has direct implications for the immune response that impacts the development of IBD. The complexity of IBD pathogenesis, involving multiple distinct elements, suggests the need for an integrative approach, likely utilizing computational modeling of molecular datasets to identify more specific therapeutic targets.

Keywords: epigenetics; gut dysbiosis; immunomodulation; inflammation; inflammatory bowel disease.

Figure 1

The role of gut dysbiosis in the pathogenesis of inflammatory bowel disease. Gut microbiota reflect an interaction of host genetics with dynamic exposure to innumerable stimuli from the exposome. Crosstalk amongst these factors results in long-standing consequences to the gut microbiota and epigenetic modifications in a multidirectional fashion, potentially affecting susceptibility to diseases. The prevalence of either regulatory (eubiosis) or inflammatory (dysbiosis) species within the gut microbial community determines the respective predominant immune response. Treg, regulatory T-cell; Breg, regulatory B-cell; ILC, innate lymphoid cell; IgA, immunoglobulin A; MØ, macrophage; TSLP, thymic stromal lymphopoietin.