The role of bitter taste sensing in food allergies

苦味感应在食物过敏中的作用

• 批准号: 10004492
• 负责人: WILLIAM KHOURY-HANOLD
• 金额: $ 7.5万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004492
• 关键词: Accident and Emergency department; Adherence; Adult; Affect; Agriculture; Allergic; Allergic Disease; Allergic inflammation; Anaphylaxis; Antibody Formation; Antibody Response; Antigen Presentation; Attenuated; B-Cell Activation; B-Lymphocytes; Biological Models; Cell Culture Techniques; Cells; Child; Consumption; Data; Dendritic Cells; Dendritic cell activation; Development; Diet; Disease; Endocrine; Enteroendocrine Cell; Environmental Risk Factor; Epithelial; Epithelial Cells; Esthesia; Etiology; Exposure to; Fatty acid glycerol esters; Flow Cytometry; Food; Food Hypersensitivity; Food Supply; Gastrointestinal tract structure; Genetic Transcription; Goals; Healthcare Systems; Hormones; Hypersensitivity; Immune response; Immune system; Immunoglobulin Class Switching; Immunoglobulin Switch Recombination; In Vitro; Individual; Ingestion; Intervention; Intestines; Life; Macronutrients Nutrition; Measures; Medical; Mediterranean Diet; Micronutrients; Minerals; Modality; Modernization; Mus; Oral; Phytochemical; Plants; Population; Prevalence; Prevention; Production; Research; Risk; Role; Sensory; Shapes; Signal Pathway; Signal Transduction; Small Intestines; Structure; T-Cell Activation; T-Lymphocyte; Taste Buds; Taste Perception; Techniques; Testing; Tissues; United States; Vitamins; allergic response; antigen challenge; avoidance behavior; base; cell type; cost; denatonium benzoate; dietary guidelines; experimental study; fast food; food allergen; food science; fruits and vegetables; in vitro Assay; in vitro Model; in vivo; individual response; intestinal epithelium; lifestyle intervention; migration; oral tolerance; prevent; response; single-cell RNA sequencing

7. Project Summary/Abstract The prevalence of food allergies has increased dramatically in the United States and around the world. Given the rate at which allergic disease has increased, multiple environmental factors, including changes to our diet, are likely culprits. For example, increased consumption of fruits and vegetables and adherence to a Mediterranean diet decreases the risk of allergic disease while diets high in fat and fast foods increase this risk. However, the role of non-nutritive components, such as bitter tasting phytochemicals, in the development or prevention of food allergies is not known. Bitter tasting phytochemicals were once ubiquitous in our diets but modern agriculture and food science techniques have all but eliminated them from most of our food supply. Therefore, it is paramount that we understand how their absence in our modern diet shapes the intestinal immune system and affects the development of food allergies. This project will investigate how sensory epithelial cells in the gastrointestinal tract sense bitter tastants and how they integrate this information with other sensory modalities to evaluate the overall quality of the ingested food. Specifically, we will use an in vitro model system to study enteroendocrine cell responses to varying ratios of bitter tastants to macronutrients. Complementary to these studies, we propose to use single cell RNA sequencing to measure rare epithelial cell types’ responses to bitter tastants in vivo. We will also study how bitter tastant sensing in the gut shapes the composition of the immune system and how this affects the development of allergic disease. Specifically, we will use a combination of flow cytometry, qPCR, and in vitro models to investigate dendritic cells, T cells, and B cells in the small intestine and their activation, migration, and effector functions in response to bitter tastant sensing at steady state and in the context of allergic inflammation. The potential impact of this research will be the development of dietary guidelines and medical interventions that take into account the non-nutritive components of our food such as phytochemicals and bitter tastants.

7.项目总结/摘要 食物过敏的流行在美国和世界各地急剧增加。给定 过敏性疾病增加的速度，多种环境因素，包括我们饮食的变化， 很可能是罪魁祸首。例如，增加水果和蔬菜的消费， 地中海饮食减少了过敏性疾病的风险，而高脂肪饮食和快餐则增加了这一风险。 风险然而，非营养成分，如苦味植物化学物质，在发育中的作用， 或食物过敏的预防是未知的。苦味的植物化学物质曾经在我们的饮食中无处不在， 现代农业和食品科学技术几乎已经将它们从我们的大部分食品供应中消除。 因此，至关重要的是，我们要了解它们在现代饮食中的缺失是如何影响肠道功能的。 免疫系统和影响食物过敏的发展。 这个项目将研究胃肠道中的感觉上皮细胞如何感知苦味剂， 他们如何将这些信息与其他感官形式相结合，以评估摄入的整体质量 食物具体来说，我们将使用体外模型系统来研究肠内分泌细胞对不同的 苦味促味剂与大量营养素的比例。作为这些研究的补充，我们建议使用单细胞RNA 测序以测量罕见的上皮细胞类型对体内促苦味剂的反应。我们还将研究如何 肠道中的苦味剂感知塑造了免疫系统的组成，以及这如何影响免疫系统。 过敏性疾病的发展。具体而言，我们将使用流式细胞术、qPCR和体外细胞培养的组合。 研究小肠中树突状细胞、T细胞和B细胞及其活化、迁移 以及在稳态和过敏性环境中响应于苦味促味剂感知的效应器功能 炎症这项研究的潜在影响将是膳食指南和医疗保健的发展。 考虑到我们食物中的非营养成分，如植物化学物质和苦味， 促味剂