The impact of intestinal inflammation on the nutritional environment of the gut microbiota

Abstract

The intestinal epithelium is a single cell barrier separating a sterile mucosal tissue from a large microbial community dominated by obligate anaerobic bacteria, which inhabit the gut lumen. To maintain mucosal integrity, any breach in the epithelial barrier needs to be met with an inflammatory host response designed to repel microbial intruders from the tissue, protect the mucosal surface and repair injuries to the epithelium. In addition, inflammation induces mechanisms of nutritional immunity, which limit the availability of metals in the intestinal lumen, thereby imposing new selective forces on microbial growth. However, the inflammatory host response also has important side effects. A by-product of producing reactive oxygen and nitrogen species aimed at eradicating microbial intruders is the luminal generation of exogenous electron acceptors. The presence of these electron acceptors creates a new metabolic niche that is filled by facultative anaerobic bacteria. Here we review the changes in microbial nutrient utilization that accompany intestinal inflammation and the consequent changes in the composition of gut-associated microbial communities.

Keywords: Anaerobic respiration; Intestinal inflammation; Microbiota; Nutritional immunity.

Figure 1

The inflammatory host response creates a new metabolic niche in the intestine. (A) The metabolic niche occupied by obligate anaerobic bacteria in the healthy intestine. Clostridia and Bacteroidia degrade complex carbohydrates and proteins in the distal gut to form a variety of metabolic end products, which accumulate in the lumen [32]. Furthermore, the head groups of phospholipids released by sloughing are degraded to TMA and ethanolamine [63]. Hydrogen produced by Clostridia and Bacteroidia fuels the growth of sulfate-reducing bacteria (Desulfovibrio), which produce hydrogen sulfide [35-37], a toxic gas oxidized by colonocytes to form harmless thiosulfate [38,39]. Butyrate is a fermentation product of obligate anaerobic bacteria that serves as nutrient for colonocytes [34]. (B) The metabolic niche occupied by facultative anaerobic Enterobacteriaceae in the healthy intestine. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by the inflammatory host response oxidize luminal compounds (TMA and thiosulfate) to form exogenous electron acceptors (trimethylamine N-oxide [TMAO] and tetrathionate, respectively) [40,48,49]. Some RNS species are converted into the exogenous electron acceptor nitrate in a reaction catalyzed by carbon dioxide (CO₂) [45]. The presence of exogenous electron acceptors enables Enterobacteriaceae to utilize microbiota-derived metabolic end products to generate energy, maintain redox balance and acquire carbon for the biosynthesis of primary metabolites.