Grant: Project Grant

There is increasing evidence that interactions between host intestinal tissues with specific commensal microbes or pathogens can alter the effectiveness or toxicity of drugs. Some reports, including our previous studies, have found that the resident commensal bacteria can directly alter the absorption or elimination of drugs by using their own enzymatic machinery. However, considerably less is known about how commensal microbes or pathogens can interact with the host tissues to activate specific immune pathways and alter the metabolism of orally administered drugs. In the current proposal, we seek to build on our strong preliminary data to better understand how host-microbe/pathogen interactions and the activation of the immune system within the intestinal alters drug metabolism through an IL-22-dependent process. The findings of our study will provide significant insight into how adverse drug responses might be triggered in the context of intestinal inflammation and may provide the impetus to modify clinical dosing regimens to address alterations in intestinal first-pass metabolism.