Grant: Project Grant

Our lower bowel harbors a dense, complex community of microbes known as the human gut microbiota (HGM). The HGM plays a key role in our health because it enables us to obtain nutrition from otherwise indigestible polysaccharides from fruits and vegetables that comprise "dietary fibre". The ability of bacteria in the HGM to metabolise plant polysaccharides results from specialized enzymes - glycosidases - that are not produced by our own bodies. In this project, we will use our specialist knowledge of HGM enzymes to develop a new route to deliver drugs directly to the lower gastrointestinal tract, to improve the treatment of inflammatory bowel diseases (IBD), e.g. Crohn's disease and ulcerative colitis. The efficacy and safety of many IBD drugs is limited by absorption in the stomach and small intestine, which causes these drugs to circulate throughout the body. By connecting key IBD drugs to a large, hydrophilic vegetable carbohydrate through a specific chemical bond - a technique we call "GlycoCaging" - general absorption in the GI tract will be prevented. However, once this conjugate reaches the lower GI tract, where our HGM resides, bacterial glycosidases will cleave the chemical bond, releasing the cargo as the free drug. This microbiota-mediated release will maximize the local dose and efficacy of the drug while minimizing systemic uptake and side-effects. The incidence of IBD is rising globally and there is an especially high prevalence among Canadians (ca. 1 in 120 individuals). The new GlycoCaged versions of established and emerging IBD drugs to be developed in this project may lead to a new treatment paradigm and represent a made-in-Canada solution to alleviate the suffering of individuals with IBD and other GI diseases.