The Home Mycobiome and Childhood Asthma

家庭真菌组和儿童哮喘

基本信息

批准号：
10229176
负责人：
JOANNE ELAINE SORDILLO
金额：
$ 48.11万
依托单位：
HARVARD PILGRIM HEALTH CARE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10229176
关键词：
Activities of Daily Living Adverse effects Affect Age Airway Disease Allergens Allergic Disease Allergic rhinitis Anabolism Asthma Bacteria Biological Birth CD4 Positive T Lymphocytes Cell Wall Cells Characteristics Child Childhood Childhood Asthma Chitin Chronic Disease Coculture Techniques Cohort Studies Communities Complex Conflict (Psychology)Data Dendritic Cells Development Disease Outcome Epidemiology Experimental Animal Model Experimental Models Exposure to FOXP3 gene Genes Glucans Health Home environment House Dust Human Human Microbiome Hypersensitivity IL2RA gene Immune Immune response Immune system Immunization In Vitro Incidence Infant Interferon Type II Interleukin-4 Joints Knowledge Life Lung diseases Mannans Microbe Molecular Outcome Participant Phenotype Play Predisposition Production Reporting Research Risk Role Sampling Shapes Soil Source Stimulus T cell response Taxonomy Techniques Testing Validation Wheezing Yeasts airway inflammation allergic airway disease bacterial community base beta-Glucans cohort disorder risk early life exposure epidemiologic data experimental study fungus genetic signature gut colonization immune function immunoregulation in vitro Model in vitro testing infancy member microbial microbiome microbiome research mycobiome prospective protective effect rRNA Genes response secondary analysis targeted sequencing

项目摘要

PROJECT ABSTRACT Early life exposures are known to alter the risk of asthma, a chronic disease of the airways that affects 6 million children in the U.S. Environmental microbes may contain taxa that “prime” the immune system to decrease asthma susceptibility, while other taxa may instead enhance allergic disease response. Environmental microbiome studies have developed in parallel to those of the human microbiome, with a spotlight on bacteria, and little to no emphasis on fungi. Research into the role of environmental fungal communities (the “mycobiome”) in allergic disease development represents an untapped domain with high potential knowledge gains, given that fungal communities are rich sources of innate immune stimuli, allergens and biologically active metabolites, the potency of which vary significantly by taxa. We hypothesize that the relationship between early life exposure to the home fungal mycobiome and allergic disease risk depends upon the specific taxonomic composition of the fungal community, its capability to produce particular types of immune-stimulatory cell wall components, and its production of secondary metabolites. For this study, we will use home environmental samples (house dust) and longitudinal allergic disease outcome data from the The Epidemiology of Home Allergens and Asthma Study (EHAAS) cohort. In specific aim 1, we will perform targeted (ITS) sequencing to identify home fungal communities and their specific taxonomic members associated with pediatric airway and allergic disease risk. In specific aim 2, we will relate gene signatures of biologically active fungal cell wall components and fungal secondary metabolites to respiratory and allergic disease outcomes. In specific aim 3, we will test “protective” fungal taxa, protective metabolites and house dust extracts enriched for multiple protective components in an immune cell in vitro model.

项目摘要已知早期生活暴露会改变哮喘的风险，哮喘是一种气道的慢性疾病影响美国环境微生物的600万儿童可能包含“主要”的分类单元免疫系统可降低哮喘感染率，而其他分类单元可能会增强过敏性疾病反应。人类微生物组的那些，对细菌的关注点，几乎没有强调真菌。研究环境真菌社区的作用疾病发展代表一个尚未开发的领域，具有很高的潜在知识收益，鉴于真菌群落是先天免疫刺激，过敏原和生物活性的代谢物，其效力因分类群而异早期生命暴露于家庭真菌真菌过敏性过敏性之间的关系疾病的风险取决于真菌社区的分类合成综合，其产生特定类型的免疫刺激性细胞壁成分的能力，其能力生产次级代谢物。（房屋灰尘）和纵向杀伤性疾病结果数据家用过敏原和哮喘研究（EHAAS）在特定目标中。（其）测序以识别家庭真菌群落及其特定的分类成员在特定目标中，小儿气道和过敏疾病风险相关。生物活性真菌细胞壁成分和真菌二级代谢产物的特征在特定目标中，我们将测试“保护性”真菌分类单元，保护性代谢物和房屋灰尘提取物富含多个保护剂免疫细胞中的成分体外模型。