Grant: Operating Grant

The human gut is colonized by a vast population of microorganisms, known collectively as the microbiota. When in balance, this complex ecosystem positively affects human health by enabling us to obtain energy from the otherwise indigestible complex carbohydrates known as "dietary fibre", while at the same time providing protection from pathogens and disease. And although it is clear that the breakdown of dietary fibre both fuels the microbiota and provides up to 10% of our daily calories, very little is actually known about this process on the molecular level. Large-scale gene sequencing is currently providing an increasingly detailed picture of which organisms are abundant in healthy gut microbiota and what genetic information they possess. However, our understanding of the complex interplay of proteins and enzymes encoded by this genetic information, which are the biocatalysts ultimately responsible for turning dietary fibre into simple sugars, is only in its infancy. Indeed, the pathways by which many of the most common dietary polysaccharides are metabolized by the gut microbiota are currently not known. This research program will address this knowledge gap through detailed biochemical, protein structural, and genetic analysis of coordinated systems of genes from predominant human gut bacteria, which are implicated in dietary fibre metabolism. The key outcomes of the research will include providing new insight into the basic function of the microbiota in our bodies. In turn, this will inform novel strategies to improve human nutrition and health through specific dietary intervention or microbial treatments to upgrade or "reboot" our natural microflora.