Microenvironmental Factors that Shape Bacterial Metabolites in Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a significant global health problem that involves chronic intestinal inflammation and can involve severe comorbidities, including intestinal fibrosis and inflammation-associated colorectal cancer (CRC). Disease-associated alterations to the intestinal microbiota often include fecal enrichment of Enterobacteriaceae, which are strongly implicated in IBD development. This dysbiosis of intestinal flora accompanies changes in microbial metabolites, shaping host:microbe interactions and disease risk. While there have been numerous studies linking specific bacterial taxa with IBD development, our understanding of microbial function in the context of IBD is limited. Several classes of microbial metabolites have been directly implicated in IBD disease progression, including bacterial siderophores and genotoxins. Yet, our microbiota still harbors thousands of uncharacterized microbial products. In-depth discovery and characterization of disease-associated microbial metabolites is necessary to target these products in IBD treatment strategies. Towards improving our understanding of microbiota metabolites in IBD, it is important to recognize how host relevant factors influence microbiota function. For example, changes in host inflammation status, metal availability, interbacterial community structure, and xenobiotics all play an important role in shaping gut microbial ecology. In this minireview, we outline how each of these factors influences gut microbial function, with a specific focus on IBD-associated Enterobacteriaceae metabolites. Importantly, we discuss how altering the intestinal microenvironment could improve the treatment of intestinal inflammation and associated disorders, like intestinal fibrosis and CRC.

Keywords: Escherichia coli; colorectal cancer; inflammation; inflammatory bowel disease; metabolites; metal; microbiota; therapeutics.

Figure 1

Intestinal microenvironmental stressors that influence bacterial metabolite production and disease on the host. During inflammation, increased epithelial oxygenation and mucus degredation is linked to a loss of gut microbial diversity and enrichment of Enterobacteriaceae, notably Escherichia coli. E. coli at the mucosal interface and within intestinal tissue respond to microenvironmental changes, which alters their disease-causing potential. Important factors affecting E. coli metabolite production in the gut include host inflammation, nutritional immunity, interbacterial interactions, and exogenous pharmaceuticals.