PNNL

Abstract

We propose the development and application of a microtiter plate-based chemical probe assay that can facilitate the rapid quantification of fecal microbiome-associated enzyme functional activities (“gut pharmacomicrobiomics”). Our initial proof-of-concept project with FedImpact is to show that one or more glucuronidase probes can be used for sensitive and reproducible characterization of fecal microbe glucuronidase activities. Glucuronidase enzymes are important for contributing to enterohepatic recycling of therapeutic drug compounds, resulting in impaired or prolonged drug activity. Importantly, the assay to be developed will permit facile ‘swapping’ of chemical probes to characterize different and multiple enzyme activities. Similarly, the assay is naïve to the biological sample to be analyzed.