Food, drugs, and bugs: A metagenomic view of pharmacology

Our gastrointestinal tracts harbor complex microbial communities (the gut microbiome) that are capable of a vast array of enzymatic activities, contributing to the metabolism of our diet and the drugs we take. Yet the molecular mechanisms responsible often remain unknown, making it challenging to translate these findings to new therapies and diagnostics, or to appreciate their broader biological, ecological, and evolutionary implications. We are studying the interactions between gut microbes and xenobiotics, including host-targeted drugs (e.g., the cardiac drug digoxin) and diet-derived bioactive compounds (e.g., polyphenols). I will discuss two ongoing projects in the lab. First, we have identified a cytochrome-encoding operon responsible for the bacterial inactivation of digoxin, inhibited by arginine in vitro and in vivo, absent in nonmetabolizing E. lenta strains, and predictive of digoxin inactivation by the human gut microbiome. Second, we have shown that food-derived compounds reshape the gut microbiota in a manner that may protect against metabolic syndrome. Ultimately, we aim to obtain a more comprehensive view of human metabolism, yielding fundamental insights into host-microbial interactions, and supporting translational efforts to predict and manipulate the metabolic activities of our resident gut microbes.