Grant: Discovery Grants Program - Individual

Canada faces significant challenges from chronic disease epidemics, which are directly or indirectly linked to the human diet. The regular consumption of fruits and vegetables has been consistently associated with the promotion of beneficial physiological functions. These health benefits have been attributed to biologically active polyphenols, especially flavonoids. A class of polymerized flavonoids, proanthocyanidins, represent over 50% of dietary polyphenols consumed; however, these proanthocyanidins are poorly absorbed in the small intestine and therefore their beneficial effects are exerted via the colonic microflora of individuals. My Discovery Grant research revealed that highly polymeric proanthocyanidins can be toxic but they can be bioconverted into safe and beneficial metabolites using probiotic bacteria. Importantly, some probiotic metabolites of proanthocyanidins exhibited the ability to prevent DNA damage by carcinogens. The overall goal of the research program is to elucidate the mechanisms of action of dietary flavonoids and their metabolites in relation to specific physiological functions. In the next five years, we will further uncover the structure-function (including toxicity) relationship of proanthocyanidins and molecular mechanisms of probiotic metabolites of proanthocyanidins to enhance our antioxidant machinery through modulation of cellular signaling pathways using cultured healthy cells. For the first time, we will study how these metabolites can activate a unique transcription factor called Nrf2, which is the master regulator of our antioxidant defence system. New knowledge of probiotic species specific to bioconversion and proanthocyanidin profiles in Canadian bioresources will be established. Innovative new agri-food processing technologies will be developed for efficient and sustainable bioconversion of proanthocyanidins extracted from underutilized Canadian bioresources and prebiotic fiber-based encapsulation technology to manufacture novel functional ingredients. Highly qualified personnel will be trained in emerging interdisciplinary areas of nutritional metabolomics of food bioactives. The new knowledge generated through this research program will directly contribute to the development of novel flavonoid-inspired functional foods and nutraceuticals that will reduce the risk of chronic diseases in humans and companion animals. The research outcome will immensely advance the fundamental knowledge needed to develop effective non-synthetic (nature-derived) agents to combat DNA damage and contribute to cancer chemoprevention. Proanthocyanidins can be developed as a second-generation prebiotic along with probiotic bacteria. Underutilized Canadian agro-industrial and forestry waste can be turned into a valuable source of novel healthy food, functional ingredients or nutraceuticals, and in turn, these may contribute to reducing economic burdens associated with chronic disease incidence and mortality in our society.