Grant: Project Grant

Our lower bowel harbors a dense, complex community of microbes known as the human gut microbiota (HGM). A well-balanced HGM is central to our health because it enables us to obtain nutrition from otherwise indigestible polysaccharides that comprise "dietary fibre", while at the same time protecting us from pathogens and disease. However, the fundamental microbiology and biochemistry of this process is unknown for many of our most important bacterial residents. This lack of information limits our ability to improve our health through dietary and microbial approaches. Members of the genus Prevotella predominate in the HGM of individuals who consume plant-rich diets associated with a healthy lifestyle, including vegetarian, rural, and Indigenous people. Prevotella-rich HGM are associated with several beneficial effects, including increased insulin sensitivity and glucose tolerance (anti-diabetic properties) and a reduction in opportunistic pathogens. With rising incidences of metabolic and other diseases associated with post-industrial Western diets, which in contrast are dominated by Bacteroides species, it is urgent to understand the factors which favor Prevotella growth in the HGM. This research project will address the current knowledge gap in our understanding of HGM metabolism through in-depth functional characterization of several polysaccharide-specific gene clusters in the exemplary species Prevotella copri vis-à-vis Bacteroides ovatus. Together with growth studies on complex media, these results will provide an unprecedented molecular picture of how Prevotella prioritize access to individual carbohydrates in dietary fiber leading to competitive fitness. In turn, this holistic understanding will inform personalized HGM analysis and the development next-generation microbial ecosystem therapies to improve human health.