Grant: Fellowship - Priority Announcement: Gastroenterology

The intestine is home to over 100 trillion bacteria cells that combine to make up the gut microbiota. The composition of the gut microbiota varies between individuals and like a fingerprint, no two individuals have the same microbiota. The gut microbiota helps its host by performing a number of functions ranging from digestion to development of the immune system. Recent research suggests that the microbiota can also influence the effectiveness of widely used drugs and medications, but how this occurs is not understood. Evidence from our lab suggests that the microbiota can 'communicate' with chemical receptors in the intestine, termed xenobiotic receptors, to control enzymes that determine how fast drugs are metabolized and thus, how quickly they become ineffective. Therefore, we hypothesize that distinct microbiota differentially modulate xenobiotic signaling and host drug-metabolism profiles to influence drug activity. By introducing different types of bacteria into mice, and examining the ability of different microbiotas to influence xenobiotic receptor function, we will determine how microbes affect drug metabolism. We will also examine how differences in the microbiota control why some people respond to drugs treatments while others do not. An understanding of how the microbiota can influence drug metabolism will offer insight into how modulating the microbiota can make drugs more effective. This offers a novel approach to personalized medicine, whereby targeting the microbiota in calculated ways will optimize the efficacy of current drug-based treatments including those for inflammatory bowel disease, hypertension, and diabetes.