Biomarkers of Atopy Beginning Early (BABE)

特应性早期开始的生物标志物 (BABE)

• 批准号: 10633364
• 负责人: Kirsi Jarvinen-Seppo
• 金额: $ 145.75万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-07 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633364
• 关键词: 5 year old; Allergens; Allergic; Allergic Disease; Asthma; Atopic Dermatitis; Bathing; Bioinformatics; Biological Markers; Birth; Blood; Cells; Child; Childhood; Clinical Data; Cluster Analysis; Cohort Studies; Consumption; Data; Development; Diet; Disease; Eating; Epithelial Cells; Europe; Exposure to; Extrinsic asthma; Family; Farm; Feces; Food Hypersensitivity; Foundations; Funding; Future; Generations; Grant; Home; Homing; House Dust; Human; Hypersensitivity; Immune; Immune response; Immune system; Immunologic Markers; Impairment; Incidence; Individual; Infant; Inflammation; Inflammatory; Infrastructure; Innate Immune System; Knowledge; Lead; Life; Life Style; Livestock; Memory; Mennonite; Milk; Natural Immunity; North America; Permeability; Population; Prevention; Production; Regulatory T-Lymphocyte; Risk; Sampling; Skin; Swab; T-Lymphocyte; T-Lymphocyte Subsets; TSLP gene; Testing; Training; Tryptophan; Volatile Fatty Acids; adaptive immunity; atopy; biobank; biomarker identification; clinical development; cohort; comparison group; cytokine; data management; early childhood; early onset; food allergen; gut microbiome; high risk; high risk infant; individualized prevention; infancy; infant gut microbiome; metabolome; metagenomic sequencing; microbial; microbiome; microbiome composition; monocyte; organizational structure; preservation; programs; recruit; respiratory; sample collection; skin barrier; skin microbiome; transcriptome; transcriptomics; unpasteurized; urban children

PROJECT SUMMARY/ABSTRACT – OVERALL Atopic dermatitis (AD) often precedes sensitization to food allergens and the development of clinical food allergy (FA) due to compromised skin barrier function allowing allergen sensitization through skin. A large body of data from Europe and North America suggest that living on farms is associated with a decreased risk of asthma and atopic diseases. Asthma has been a focus of farming lifestyle studies; however, little is known about the protective mechanisms of farming lifestyle on development of AD and FA which often precede respiratory allergies and asthma. The farm lifestyle protection against allergic diseases comprises likely three prerequisites: 1) innate immune training and a modified immune response upon re-exposure, 2) generation of suppressive regulatory T cells, and 3) preserved barrier function. Here, we propose to assess these preconditions in an extended longitudinal birth cohort study among the Old Order Mennonites (OOM), a population practicing traditional, single-family farming with a lower rate of asthma and allergic diseases, including atopic dermatitis and food allergies in early childhood. Biomarkers of Atopy Beginning Early (BABE) will test the overall hypothesis that perturbed skin barrier function, immune millieu and microbiome drive the development of atopic dermatitis, Th2 inflammation, allergic sensitization and FA, whereas a healthy gut microbiome modulates the protective metabolite pool such as short chain fatty acids and tryptophan metabolites and protective Treg immune development. Project 1 utilizes deep metagenomic sequencing to assess infant gut microbiome composition and corresponding metabolome to show that OOM infant gut microbiome is distinct from urban infants. Project 2 assesses markers of allergic sensitization and protective immune development utilizing multiparameter spectral flow, unbiased clustering analysis and transcriptomic studies to demonstrate that urban infants have a higher number of hyperinflammatory monocytes and Th2-skewed T cell subsets detected in early infancy, whereas OOM have gut-homing memory Tregs. Project 3 will characterize skin barrier function, microbiome and immune cell transcriptome. Our longitudinal birth cohort ZOOM1, funded by a U01 grant, is now 2-5 years old and is a shared foundation for the three projects (78 OOM and 79 urban). We will add another 120 infants as a ZOOM2 cohort (80 urban and 40 OOM). We will also replicate key T cell biomarkers in larger infant cohorts (Start Eating Early Diet ”SEED” and Microbiome and Allergic Asthma Precision Prevention “MAAP2”). The infrastructure to recruit, collect and share samples and data is provided by the Cohort Admin & Biorepository and Data Management & Bioinformatics Cores. The Admin Core will provide overall financial and administrative infrastructure. These studies aim to identify biomarkers, mechanisms, and protective strategies against atopic and food allergy.

项目概要/摘要——总体 特应性皮炎 (AD) 通常先于对食物过敏原的过敏和临床食物过敏的发展 （FA）由于皮肤屏障功能受损，导致过敏原通过皮肤过敏。 来自欧洲和北美的研究表明，住在农场可以降低患哮喘和哮喘的风险 特应性疾病一直是农业生活方式研究的焦点；然而，人们对它知之甚少。 农业生活方式对 AD 和 FA 发生的保护机制，这些疾病通常先于呼吸道疾病 过敏和哮喘。预防过敏性疾病的农场生活方式可能包括三个先决条件： 1) 先天免疫训练和重新暴露后的改良免疫反应，2) 抑制性免疫反应的产生 调节性 T 细胞，以及 3) 保留的屏障功能在这里，我们建议评估这些先决条件。 旧秩序门诺派（OOM）的扩展纵向出生队列研究，这是一个从事实践的人群 传统的单户农业，哮喘和过敏性疾病（包括特应性皮炎）的发病率较低 儿童早期的食物过敏生物标志物早期开始（BABE）将测试整体。 假设皮肤屏障功能、免疫环境和微生物群受到干扰会导致特应性过敏的发生 皮炎、Th2 炎症、过敏性致敏和 FA，而健康的肠道微生物群则可调节 保护性代谢池，例如短链脂肪酸和色氨酸代谢物以及保护性 Tregs 项目 1 利用深度宏基因组测序来评估婴儿肠道微生物组。 组成和相应的代谢组表明 OOM 婴儿肠道微生物组与城市婴儿肠道微生物组不同 项目 2 利用婴儿过敏性致敏和保护性免疫发育的标志物进行评估。 多参数谱流、无偏聚类分析和转录组学研究证明城市 婴儿早期检测到的高炎症单核细胞和 Th2 偏向 T 细胞亚群数量较多 婴儿期，而 OOM 具有肠道归巢记忆 Tregs，项目 3 将表征皮肤屏障功能， 我们的纵向出生队列 ZOOM1 由 U01 拨款资助。 现在已有 2-5 年历史，是三个项目（78 OOM 和 79 城市）的共享基础。我们将添加另一个项目。 120 名婴儿作为 ZOOM2 队列（80 名城市婴儿和 40 名 OOM）我们还将在更大的样本中复制关键 T 细胞生物标志物。 婴儿队列（开始早期饮食“SEED”和微生物组和过敏性哮喘精准预防 “MAAP2”）。招募、收集和共享样本和数据的基础设施由队列管理员提供。 生物储存库和数据管理与生物信息学核心将提供整体财务和信息。 这些研究旨在确定生物标志物、机制和保护策略。 对抗特应性和食物过敏。