Allergen processing by human gastrointestinal microbiota

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Background. The human gastrointestinal tract is constantly exposed to dietary allergens. Before interacting with the immune system, food allergens need to resist harsh conditions in the gut lumen such as low pH, bile acids and digestive and microbial enzymes. While the gastrointestinal digestion of allergens by mammalian enzymes has been extensively characterized, the metabolic processing by human microbiota, and how this influences its ability to access the immune system, has yet to be elucidated. Programmatic: We plan to establish a program that studies the interaction between microbes and common dietary allergens. The long-term goal is to determine the main pathways of biochemical processing of allergens by human microbiota. Our research seeks to further our understanding of fundamental microbial processes involved in the metabolism of allergens. Short-term goals: We will first focus on the metabolism of peanut (PN). PN is highly stable under oro-gastrointestinal digestion conditions and major allergens are resistant to mammalian enzymes. Surprisingly, the impact of microbial metabolism on PN remains unexplored. Therefore, the short-term goal of our proposal is to identify microbial enzymes with high metabolic capacity against PN and characterize its impact on PN immunogenicity as well as mucosal and systemic absorption. This goal is unfolded in 3 aims: -Aim 1: To identify microbial enzymes with PN-degrading capacity. We hypothesize that the human gastrointestinal tract harbours microbes that modify the main PN allergens. -Aim 2: To characterize PN immunogenicity and intestinal uptake after microbial metabolism in vitro. We hypothesize that microbes modify PN, which alters its immunogenicity and passage through the mucosa. -Aim 3: To assess the ability of microbes to alter systemic access of allergens in vivo. We hypothesize that microbes modify mucosal absorption and systemic access of PN. Impact. Our program will contribute to reach a better understanding on the role of microbes in food allergies, which affect >2.5 million people in Canada. The short-term goal will characterize allergen stability from a novel angle based on the metabolic capacity of microbes and identify enzymes with the capacity to degrade PN. The development of a microbial biochemistry approach for the removal of PN may be useful because of the high rate of accidental allergen exposures (33% of PN-allergic patients suffer, at least, one accidental exposure yearly) and economic cost ($764 million to cover emergencies in the USA). The enzymes identified here may be commercialized for the removal of PN in the household environment and food preparation industry. The knowledge and methodology applied here could be extended to other food allergens (shellfish, nuts, wheat) in future applications. Implementing this research in other food sensitivities would have an outstanding impact as it is estimated that 20% of the population experience adverse reactions to food.