Mechanisms of inflammation-driven bacterial dysbiosis in the gut

Abstract

The gut microbiota has diverse and essential roles in host metabolism, development of the immune system and as resistance to pathogen colonization. Perturbations of the gut microbiota, termed gut dysbiosis, are commonly observed in diseases involving inflammation in the gut, including inflammatory bowel disease, infection, colorectal cancer and food allergies. Importantly, the inflamed microenvironment in the gut is particularly conducive to blooms of Enterobacteriaceae, which acquire fitness benefits while other families of symbiotic bacteria succumb to environmental changes inflicted by inflammation. Here we summarize studies that examined factors in the inflamed gut that contribute to blooms of Enterobacterieaceae, and highlight potential approaches to restrict Enterobacterial blooms in treating diseases that are otherwise complicated by overgrowth of virulent Enterobacterial species in the gut.

Figure 1

Mechanisms of inflammation-driven blooms of Enterobacteriaceae in the gut. (1) Superoxide radicals and nitric oxide react to give rise to nitrate (NO₃⁻), which can be reduced by nitrate reductase-expressing Enterobacteriaceae in anaerobic nitrate respiration. (2) Higher levels of oxygen in the inflamed gut permit aerobic respiration by Enterobacteriaceae, while inhibiting growth of obligate anaerobes Bacteroidia and Clostridia. (3) Phospholipids from dying epithelial cells are broken down to give rise to ethanolamine, which is converted to ammonia that can be utilized in tricarboxylic acid cycle, glyoxylate cycle and lipid biosynthesis. (4) The release of sialic acid from MUC2 is mediated by cecal sialidase activity from Bacteroides vulgatus, and Enterobacteriaceae can take up sialic acid for synthesis of bacterial capsule and lipooligosaccharides. (5) Bacterial siderophore Enterobactin released by Escherichia coli inhibits the bacteriocidal effect of myeloperoxidase from neutrophils. (6) Colicin Ib (Collb)-expressing Enterobacterial species kill closely related but Collb-sensitive Enterobacterial species by releasing Collb, which forms pores in Collb-sensitive bacteria and disrupts cell wall synthesis.