Frontiers in Chemistry and Chemical Engineering

Despite the abundance and prevalence of the gut microbiota, little is known regarding the pathways and mechanisms by which these microbes affect host health. Emerging evidence suggests that many small-molecule metabolites that are produced by the gut microbiota have the ability to modulate host defense mechanisms in various inflammatory diseases. We describe amino acid-derived metabolites produced by the gut microbiota that provide colonization resistance against gastrointestinal infection with an enteric bacterial pathogen, Citrobacter rodentium (Nature 2024). In complementary work, we have also developed chemical approaches for probing the metabolic activities of biosynthetic enzymes expressed by the gut microbiota that are responsible for producing important classes of small-molecule metabolites whose metabolism is dysregulated in many inflammatory diseases (ACS Cent Sci 2019 and Manuscript in revision).