Andrew L. Goodman, Ph.D.

Research

Each of us harbors an enormous microbial community. In the gut, these microbes form a metabolic organ whose genes outnumber those in the human genome by over 100-fold, and whose composition can change overnight. It is becoming increasingly clear that variation in these communities has important consequences for health. The overall goal of the lab is to dissect the mechanisms that commensal gut microbes use to compete, cooperate, and antagonize each other in the gut and to explore how microbiome variation impacts our response to external perturbations, including pathogenic infection and medical drugs.

As an Innovation Fund investigator, Andrew L. Goodman, Ph.D., is teaming up with Ivaylo I. Ivanov, Ph.D., to test whether medical drugs and gut microbes can activate the expression of antimicrobial peptides (AMPs) in the mammalian gut that reshape the gut microbiome. In collaborative preliminary studies, the pair found that the drug digoxin selectively activates expression of an otherwise silent AMP and that this AMP eliminates specific gut microbial taxa. They also identified gut microbes that eliminate the same taxa. For this project, the pair will identify other small molecules and microbes that activate silent AMPs and assess how this activation affects microbiome composition. This research combines Goodman’s experience in anaerobic microbial genetics and biochemistry, metabolomics, and the role of the microbiome in drug metabolism and drug response with Ivanov’s expertise in mucosal immunology and the impact of the microbiome on host immunity. Findings from this work could allow the team to leverage a naturally evolved and optimized microbial control system to remodel microbiome composition.