Within the human gastrointestinal (GI) tract there reside trillions of bacterial cells (microbiota) that harbor thousands of distinct genes (microbiome). This biosphere has evolved in the context of a diverse array of diet- and host-derived small molecules to which it is chronically exposed. Consequently, gut bacteria have developed numerous enzymes to respond to this chemical deluge; however, little is known about the chemical motifs metabolized and the impacts of those metabolites on health. The Bess Lab discovers chemical reactions encoded in the microbiome and uses this repertoire to impact pharmacology through prediction of microbial metabolism of small molecules; health outcomes and communication along the gut–endocrine axis; and enzymatic production of commodity chemicals from Earth-abundant feedstocks.
Predicting gut microbiota-mediated drug metabolism to impact ADME models
A concerted effort to characterize the chemical repertoire of the microbiome is needed to understand and exploit the relationship and impact of the microbiota on pharmacology and health. We use an hypothesis-guided approach to probe the chemical-reaction space of the gut microbiome. Aiming to close the gap between drug candidates and those that enter the market, characterization of microbe-mediated metabolism will enable more accurate modeling of drug disposition, impacting current approaches to drug design.
Defining the gut microbiota's role in modulating endogenous levels of steroid hormones
Estrogens are causally linked to breast cancer incidence; however, factors impacting the inter-individual variability of circulating estrogen levels and their metabolites are poorly understood. The compositionally and functionally unique suites of bacteria residing in peoples’ GI tracts may be a crucial link between estrogen and estrogen-dependent diseases. We are elucidating the molecular mechanisms by which the gut microbiota modulates estrogen levels to provide a handle by which to alter the incidence of estrogen-dependent disease—most notably, breast cancer.
Liberate high-value chemicals from Earth-abundant resources using bacterial enzymes
Lignocellulose is among Earth’s most abundant, renewable sources of biomass. Utilization of lignocellulose has focused on separating cellulosic fibrils from lignin, channeling cellulose to biofuel and paper production—a process fueled by combusting the lignin fraction. This crude use of lignins undervalues its worth as a renewable source of aromatic commodity chemicals. We generate value-added products from lignin by identifying enzymes in ruminal bacteria capable of degrading lignin to aromatic monomers. We are also developing a novel, design-of-experiments-guided approach to enzyme engineering to modify bacterial enzymes to optimize lignin valorization.