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