Biotransformation of Xenobiotics by the Human Gut Microbiota

The human gut is home to a diverse community of microbes that can block or promote toxic effects and other bioactivities of chemicals from foods, drugs, and the environment. For example, mutagens such as heterocyclic amines in well-cooked meat, can be inactivated by microbial transformation. Bacterial metabolism can also give rise to hormone-mimicking compounds that might disrupt endocrine function.

Our work is centered on elucidating mechanisms connecting the composition of the gut microbiome of individuals with pharmaco- and toxicokinetics of gastrointestinal metabolites. This requires a quantitative assessment of microbial metabolism in anaerobic fecal batch fermentation experiments. Resulting kinetic parameters are incorporated in physiologically-based pharmacokinetic modeling and quantitative in vitro to in vivo extrapolation as alternatives to animal testing. In addition, we develop and apply mass spectrometric methodologies, biochemical techniques and in vitro toxicological assays to identify metabolite structures, active enzymes, and relate microbiome-mediated transformations with disease risk.