Grant: Discovery Grants Program - Individual

Current evidence for essential roles of gut microbe interactions with the immune system has generated strong interest in probiotics, prebiotics and dietary fibres. However, attempts to apply recent knowledge about probiotics and to manipulate gut microbes through strategic use of diet have had mixed results. Outcomes of diet-microbe based strategies not only depend on microbes, food components and the resulting microbial metabolites, but are also influenced by host factors. For example, differences between females and males in impact of prebiotics on the immune system show that sex-based factors can generate variation in outcomes of diet and gut microbe-based treatments. However, this aspect is rarely addressed in studies of prebiotics and probiotics. Other questions about use of probiotics include the impact that the foods they are consumed in have their activity. Intestinal epithelial cells (IEC) and antigen presenting cells (APC) are integral in immune activity at the intestinal interface, where they encounter gut microbes, food components and microbial metabolites. Microbial metabolites and soluble mediators are increasingly seen as key participants in effects of probiotics, diet and gut microbes on the immune system. Gaps in knowledge about the network of interactions involving probiotics, food components, microbial metabolites and host impact must be filled in order to design effective strategies for their use. IEC and APC influence innate and adaptive immunity, so are important targets of signals from probiotics, other gut microbes and dietary components. Because lactic acid bacteria (LAB) are immunomodulatory gut microbes often consumed in foods and as probiotics, they are useful tools to model gut microbe interactions with IEC and APC, and the impact of foods used for probiotic delivery. Defining mechanisms used by LAB to influence the immune system through interactions with IEC and APC is one goal of this research; another is understanding how foods commonly used to deliver probiotics affect these interactions. Other key goals are to determine differences between sexes in effects of dietary fibres and prebiotics on the immune system and on microbial metabolite production, and to use these findings to delineate the impact of microbial metabolites on IEC and APC activity. Long term goals are to facilitate effective gut microbial and food-based strategies for targeted immune outcomes. Understanding the mechanisms and interactions that drive effects of LAB, microbial metabolites and diet on the immune system will lead to optimization of their use and also to the definition of potential limitations. Trainees involved in this research will gain experience and knowledge to contribute to developing new approaches for effective use of foods and probiotics in optimizing immune activity and host defence, elements important for dietary strategies in the daily lives of Canadians.