The role of bitter taste sensing in food allergies

7.项目摘要/摘要 在美国和世界各地，食物过敏的流行率急剧上升。vt.给出 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，以及坚持 地中海饮食降低了患过敏性疾病的风险，而富含脂肪和快餐的饮食则增加了这种风险 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 或者，对食物过敏的预防尚不清楚。苦味植物化学物质曾经在我们的饮食中无处不在，但 现代农业和食品科学技术几乎从我们的大部分食品供应中消除了它们。 因此，最重要的是，我们要了解现代饮食中缺少它们是如何塑造肠道的 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觉苦味和 他们如何将这些信息与其他感官模式相结合，以评估被摄入者的整体质量 食物。具体地说，我们将使用体外模型系统来研究肠内分泌细胞对不同 苦味与常量营养素的比例。作为对这些研究的补充，我们建议使用单细胞rna 测序以测量稀有上皮细胞类型在体内对苦味的反应。我们还将研究如何 肠道中的苦味感觉塑造了免疫系统的组成，以及这如何影响 过敏性疾病的发展。具体地说，我们将结合使用流式细胞术、定量聚合酶链式反应和体外实验。 研究小肠内树突状细胞、T细胞和B细胞及其活化、迁移、 并且效应器在稳定状态和过敏的情况下对苦味的感觉作出反应 发炎。这项研究的潜在影响将是制定饮食指南和医学 考虑到我们食物中的非营养成分的干预措施，如植物化学物质和苦味 品尝者。

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.