• Introduce the role of enteric bacterial beta-glucuronidases (GUS) in triggering lower GI toxicities associated with prescription medications

• Demonstrate that GUS-targeting, small-molecule drugs can prevent these medication-induced lower GI injuries, such as chemotherapyinduced diarrhea

• Reveal the inter-individual variability among the ~300 GUS orthologs that make up the “GUSome” in the human gut microbiome

• Discuss the GUSome as a case study on the unique challenges of developing microbiome-targeting drugs

• Demonstrate the utility of a stool-based functional assay to assess patient-relevant GUSome function

• Disclose how the assay can be developed as a companion diagnostic to potentially identify patients who are responsive to GUSometargeted drugs