Andrew L. Goodman, PhD
C. N. H. Long Professor of Microbial Pathogenesis at Yale University School of Medicine and Director of the Yale Microbial Sciences Institute.
Goodman received his undergraduate degree in Ecology and Evolutionary Biology from Princeton University, his PhD in Microbiology and Molecular Genetics from Harvard University, and completed postdoctoral training at Washington University. His lab uses microbial genetics, gnotobiotics, and mass spectrometry to understand how the gut microbiome contributes to drug metabolism. The Goodman lab works to identify and characterize microbiome-encoded drug metabolizing enzymes, and to define how these microbial activities contribute to drug and drug metabolite exposure in the gut and in circulation. The lab’s contributions have been recognized by the NIH Director New Innovator Award, the Pew Foundation, the Dupont Young Professors Award, the Burroughs Wellcome Foundation, the Howard Hughes Medical Institute Faculty Scholars Program, the ASPET John J. Abel Award, and the Presidential Early Career Award in Science and Engineering.
Abstract
Oral medicinal drugs can exhibit incomplete absorption in the upper gastrointestinal tract or reach the gut after enterohepatic circulation. In these circumstances, drugs encounter enormous densities of commensal microbes, suggesting that microbiome-targeted interventions may be a means to modulate exposure to drugs and drug metabolites in the GI tract and in circulation. However, the contribution of the microbiome to these processes is largely unexplored.
I will describe examples that suggest that gut microbial activity can be responsible for a significant portion of systemic exposure to a toxic drug metabolite, even if the drug exhibits high bioavailability, if the same metabolite is readily produced by hepatic extracts in vitro, and if drug metabolite levels are low in feces. I will also introduce our efforts to explore the spectrum of microbiome-encoded drug metabolizing activities and to identify microbial genes that predict the capacity of an individual’s gut microbiome to metabolize a drug.