Regulation of Intestinal Barrier Function by Microbial Metabolites

Abstract

The human gastrointestinal tract (GI) harbors a diverse population of microbial life that continually shapes host pathophysiological responses. Despite readily available abundant metagenomic data, the functional dynamics of gut microbiota remain to be explored in various health and disease conditions. Microbiota generate a variety of metabolites from dietary products that influence host health and pathophysiological functions. Since gut microbial metabolites are produced in close proximity to gut epithelium, presumably they have significant impact on gut barrier function and immune responses. The goal of this review is to discuss recent advances on gut microbial metabolites in the regulation of intestinal barrier function. While the mechanisms of action of these metabolites are only beginning to emerge, they mainly point to a small group of shared pathways that control gut barrier functions. Amidst expanding technology and broadening knowledge, exploitation of beneficial microbiota and their metabolites to restore pathophysiological balance will likely prove to be an extremely useful remedial tool.

Keywords: Gut Barrier Function; Microbial Metabolites; Microbiota; Permeability; Tight Junction Proteins.

Figure 1

Potential treatment strategies against gut barrier dysfunction. Host-microbiota interactions and external stimuli drive changes in gut barrier integrity and lead to gut barrier dysfunction. Impaired junctional proteins and increased intestinal permeability lead to pathogen-mediated mucosal inflammation and subsequent uncontrolled immune responses mediated by macrophages, T cells, B cells, mast cells, neutrophils, and dendritic cells. Potential preventive/therapeutic interventions are shown. Inhibition of disease induced regulatory factors, hormone treatment, dietary supplementation, and healthy diets and habits can potentially restore intestinal epithelial barrier function. GJ, gap junction protein; NSAID, nonsteroidal anti-inflammatory drugs.

Figure 2

Potential pathways responsible for microbial mediated enhancement of gut barrier function. Healthy diets get metabolized by beneficial gut commensal microbiota in the human gut to produce various types of microbial metabolites such as SCFAs, indole derivatives, bile acid metabolites, conjugated fatty acids, polyamines, and phenolic derivatives. Each microbial metabolite activates various pathways responsible for modulation of gut barrier and inflammation through the activation of membrane or nuclear receptors as shown.