Metabolic Influences of Gut Microbiota Dysbiosis on Inflammatory Bowel Disease

Abstract

Inflammatory bowel diseases (IBD) are chronic medical disorders characterized by recurrent gastrointestinal inflammation. While the etiology of IBD is still unknown, the pathogenesis of the disease results from perturbations in both gut microbiota and the host immune system. Gut microbiota dysbiosis in IBD is characterized by depleted diversity, reduced abundance of short chain fatty acids (SCFAs) producers and enriched proinflammatory microbes such as adherent/invasive E. coli and H₂S producers. This dysbiosis may contribute to the inflammation through affecting either the immune system or a metabolic pathway. The immune responses to gut microbiota in IBD are extensively discussed. In this review, we highlight the main metabolic pathways that regulate the host-microbiota interaction. We also discuss the reported findings indicating that the microbial dysbiosis during IBD has a potential metabolic impact on colonocytes and this may underlie the disease progression. Moreover, we present the host metabolic defectiveness that adds to the impact of symbiont dysbiosis on the disease progression. This will raise the possibility that gut microbiota dysbiosis associated with IBD results in functional perturbations of host-microbiota interactions, and consequently modulates the disease development. Finally, we shed light on the possible therapeutic approaches of IBD through targeting gut microbiome.

Keywords: IBD; SCFAs (short chain fatty acids); dysbiosis; gut microbiota; metabolome.

FIGURE 1

Major dysbiosis of gut microbiome during IBD and its impact on worsening the condition and progression of the disease.

FIGURE 2

Proposed Host-microbe metabolic dysfunctionalities in inflammatory bowel disease. The oxidative stress environment created by inflammation acts as a selective pressure. This pressure favors the microbes that are able to resist that stress such as Proteobacteria members but not Firmicutes members. This in turn leads to less short chain fatty acids (SCFAs) production, less bile salts hydrolases (BSHs) in association with higher H₂S release. From the host side, impaired butyrate transport and oxidation, less mucin secretion, low tight junction (TJ) expression, and defective H₂S detoxification are the major host metabolic perturbations associated with IBD.