The Home Mycobiome and Childhood Asthma

家庭真菌组和儿童哮喘

• 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
• 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

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 众所周知，早期生活中的暴露会改变哮喘的风险，哮喘是一种慢性气道疾病， 环境微生物可能含有“启动”环境的分类群。 免疫系统降低哮喘易感性，而其他类群可能反而增强 过敏性疾病反应。环境微生物组研究与 人类微生物组的那些，重点是细菌，很少或根本不强调真菌。 研究环境真菌群落（“真菌群落”）在过敏性疾病中的作用 疾病发展代表了一个具有高潜在知识增益的未开发领域， 鉴于真菌群落是先天免疫刺激物、过敏原和 生物活性代谢物，其效力因分类群而显著不同。我们假设 早期生活暴露于家庭真菌菌群和过敏之间的关系 疾病风险取决于真菌群落的具体分类组成， 产生特定类型的免疫刺激性细胞壁组分的能力，及其 次级代谢产物的产生。在这项研究中，我们将使用家庭环境样本 （屋尘）和纵向过敏性疾病结局数据， 家庭过敏原和哮喘研究（EHAAS）队列。在具体目标1中，我们将执行有针对性的 (ITS)测序以鉴定家庭真菌群落及其特定的分类成员 与儿童气道和过敏性疾病风险相关。在具体目标2中，我们将基因 生物活性真菌细胞壁组分和真菌次级代谢产物的特征 呼吸道和过敏性疾病的结果。在具体目标3中，我们将测试“保护性”真菌 富含多种保护性代谢物和室内灰尘提取物 免疫细胞体外模型中的组分。