Allergen processing by human gastrointestinal microbiota

背景资料。人类的胃肠道经常暴露在饮食过敏原中。在与免疫系统相互作用之前，食物过敏原需要抵抗肠道内的恶劣条件，如低pH值、胆汁酸、消化酶和微生物酶。虽然哺乳动物酶在胃肠道消化变应原的过程已经得到了广泛的研究，但人类微生物区系的代谢过程以及这如何影响其进入免疫系统的能力尚未阐明。计划：我们计划建立一个项目，研究微生物和常见饮食过敏原之间的相互作用。长期目标是确定人类微生物区系对过敏原进行生化处理的主要途径。我们的研究试图加深我们对参与过敏原代谢的基本微生物过程的理解。短期目标：我们将首先关注花生(Pn)的代谢。PN在口腔胃肠消化条件下高度稳定，主要过敏原对哺乳动物酶具有抵抗力。令人惊讶的是，微生物代谢对净光合速率的影响仍未被研究。因此，我们建议的短期目标是鉴定对PN具有高代谢能力的微生物酶，并表征其对PN免疫原性以及粘膜和全身吸收的影响。这一目标在3个目标中展开：-目标1：鉴定具有降解PN能力的微生物酶。我们假设人类胃肠道中含有能改变主要PN变应原的微生物。目的2：体外研究PN的免疫原性和微生物代谢后的肠道摄取。我们假设微生物改变了PN，从而改变了它的免疫原性和通过粘膜的途径。-目标3：评估微生物在体内改变变应原系统通路的能力。我们假设微生物改变了PN的粘膜吸收和系统通路。冲击力。我们的计划将有助于更好地了解微生物在影响加拿大250万人的食物过敏中的作用。短期目标将从一个新的角度基于微生物的新陈代谢能力来表征过敏原的稳定性，并确定具有降解PN能力的酶。开发一种去除PN的微生物生物化学方法可能是有用的，因为意外过敏原暴露的比率很高(33%的PN过敏患者每年至少经历一次意外暴露)和经济成本(7.64亿美元用于支付美国的紧急情况)。这里确定的酶可以商业化用于去除家庭环境和食品制备行业中的PN。这里应用的知识和方法可以在未来的应用中扩展到其他食物过敏原(贝类、坚果、小麦)。在其他食物敏感性方面实施这项研究将产生显著影响，因为据估计，20%的人口对食物有不良反应。

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.