The Gut Microbiome and Inflammatory Bowel Diseases

Abstract

Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports a bidirectional relationship between disease progression and changes in microbiota membership and function. Thus, the study of the gut microbiome and host-microbe interactions should provide critical insights into disease pathogenesis as well as leads for developing microbiome-based diagnostics and interventions for IBD. In this article, we review the most recent advances in understanding the relationship between the gut microbiota and IBD and highlight the importance of going beyond establishing description and association to gain mechanistic insights into causes and consequences of IBD. The review aims to contextualize recent findings to form conceptional frameworks for understanding the etiopathogenesis of IBD and for the future development of microbiome-based diagnostics and interventions.

Keywords: dysbiosis; gut microbiota; host-microbial interactions; inflammation; inflammatory bowel diseases; pathobionts.

Figure 1.. Hypothetical model for IBD development and progression.

Under healthy conditions, commensal microbes produce beneficial metabolites to help maintain an impermeable barrier comprised of intact mucosal and epithelial layers (Panel A). IBD starts at a pre-disease state where the disease happens at a sub-clinical level. Genetic/immune drivers, environmental triggers, as well as lifestyle/diet can all contribute to the occurrence of pre-disease (Panel B). At this stage, certain commensal microbes transition to pathobionts that are more fit in an ecosystem where immune activation, the compromised barrier, mucus depletion, and other conditional factors come into play. As the disease progress, patients enter the initial stage of the disease, where patients display active inflammation mucosal damage (Panel C). The abundance of commensal bacteria significantly decreases as blooming pathobionts emerge and bloom. As a result, the microbiota produce fewer beneficial metabolites. If the condition persists for a long time, patients will reach a chronic stage of disease with persistent inflammation. The persistent inflammation and long-term dysbiosis lead to immune imbalance and the inability for mucosal healing which maintains the inflammatory and dysbiotic state creating a chronic inflammatory cycle (Panel D).