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.

项目摘要/摘要--总体 特应性皮炎(AD)通常先于对食物过敏原的致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致敏。一大堆数据 来自欧洲和北美的研究表明，住在农场与哮喘风险的降低和 特应性疾病。哮喘一直是农业生活方式研究的焦点；然而，对哮喘的研究知之甚少。 耕作生活方式对AD和FA发病的保护机制 过敏和哮喘。农场生活方式对过敏性疾病的保护可能包括三个先决条件： 1)先天免疫训练和再次暴露时的改良免疫反应，2)产生抑制 调节性T细胞；3)保护屏障功能。在这里，我们建议在一个 实践种群旧秩序门诺派(OOM)的扩展纵向出生队列研究 传统的单一家庭养殖，哮喘和过敏性疾病(包括特应性皮炎)的发病率较低 以及儿童早期的食物过敏。早期特应性疾病的生物标志物(Babe)将测试整体 特应性皮肤屏障功能紊乱、免疫功能障碍和微生物群导致特应症的假说 皮炎、Th2炎症、过敏性过敏和FA，而健康的肠道微生物群调节 保护代谢物库，如短链脂肪酸和色氨酸代谢物和保护性Treg 免疫发育。项目1利用深度元基因组测序来评估婴儿肠道微生物组 OOM婴幼儿肠道微生物组组成及相应代谢组与城市不同 婴儿。项目2评估变态反应致敏和保护性免疫发展的标志物 多参数谱流、无偏聚类分析和转录研究证明城市 婴儿早期发现高炎性单核细胞和Th2偏斜的T细胞亚群 婴儿期，而OOM有肠道归宿记忆树。项目3将描述皮肤屏障功能， 微生物组和免疫细胞转录组。我们的纵向出生队列ZOOM1，由U01赠款资助，是 现在2-5岁，是三个项目(78个OOM和79个城市)的共同基础。我们将添加另一个 120名婴儿作为ZOM2队列(80名城市婴儿和40名OOM婴儿)。我们还将复制关键的T细胞生物标记物 婴儿队列(开始吃早期饮食种子和微生物组与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和 生物仓库和数据管理&生物信息学核心。管理核心将提供总体财务和 行政基础设施。这些研究旨在确定生物标记物、机制和保护策略。 对抗特应性和食物过敏。