Role of mucin-type O-glycans in regulating commensal vs. pathologic functions of Prevotella species in IBD

Our large intestine houses trillions of bacteria comprised of hundreds of species with tremendous functional potential to promote health or chronic disease. One type of bacteria abundant in the human gut, and associated with both beneficial and harmful activities within it, is called Prevotella. Despite its abundance, what governs its healthy vs. pathogenic effects is unclear, but likely relates to the surrounding ecosystem it lives in within the gut. Prevotella thrives on sugars structures called 'glycans' present in high-fibre plant-based diets. Prevotella is also exposed to other sugars called 'O-glycans' that are found on mucus secretions from gut tissues, but how these host O-glycans affect Prevotella functions are unclear. My study proposes to test this using novel transgenic mouse lines that are impaired in their ability to produce complex O-glycoyslated mucus, and colonizing them with Prevotella species to determine whether the outcome of this symbiosis leads to healthy (mutualistic) or unhealthy (pathogenic, inflammation-inducing) physiologic responses of the gut and bacteria. These studies will be the first to directly determine what Prevotella species are most 'dangerous' to the gut, and how the gut glycosylation program controls their level of pathogenicity.