基于菌群代谢产物感应调控的虾典型过敏蛋白识别与致敏机制

近年来以虾过敏原为主要因素引发的食物过敏引起了各国政府和公众的广泛关注，成为食品安全热点问题之一。前期研究表明，虾最具代表性的典型过敏原是原肌球蛋白，如何以此为研究对象深入揭示识别和致敏分子机制中的关键科学问题对于丰富食物过敏理论和安全控制具有重要的现实意义。进一步研究证实，菌群代谢产物感应对肠道免疫微环境有重要调控作用，而肠道微环境又可影响蛋白的识别与效应。鉴于此，立足于前期的工作积累和直接的研究发现，本项目将着眼于菌群代谢产物（短链脂肪酸和氨基酸）感应及其信号通路调控，以全新视角深入解析原肌球蛋白经肠黏膜上皮和抗原递呈细胞（树突状细胞/巨噬细胞）被获取识别的特征效应和分子机制，阐明其诱导下游T细胞增殖化及致敏效应的理论。本研究旨在探究以菌群代谢产物感应调控的虾过敏蛋白识别与致敏机制，充实和完善食物过敏分子机制，为食物过敏蛋白致敏性评价体系的完善及低敏/抗敏食品的研发提供依据和支撑。

In recent years, shellfish allergies have aroused wide concerns in governments and public health worldwide, which become one of the major food safety hotspot issues. Previous studies have demonstrated tropomyosin to be the predominant shrimp allergen, so characterization of the key molecular mechanisms of allergen recognition and sensitization by focusing on tropomyosin will be of great significance for enriching food allergy theories and managing allergic problems. Additional studies have demonstrated that microbiota metabolite sensing modulates the immune microenvironment of intestine, which further regulated the recognition and function of proteins. Consequently, based on our findings of previous work, this study will focus on microbiota metabolites (mainly referred to short-chain fatty acids and amino acids) sensing and relevant regulation pathways. We intend to investigate the characteristic effects and molecular mechanisms of tropomyosin acquisition and recognition by intestinal mucous epithelium and antigen presenting cells (dendritic cells and macrophages) from a new perspective, and reveal the mechanisms of downstream T cell proliferation and allergic effects. The aim of this study is to explore the regulatory mechanisms of shrimp typical allergen recognition and sensitization by microbiota metabolite sensing. Hopefully, the improvement of molecular mechanisms of food allergy will provide scientific basis and support for renewing the food allergen evaluation system and developing hypoallergenic or anti-allergic foods.