Pets and the Infant's Microbiome Exposures: Impac on Childhood Allergic Asthma

宠物和婴儿的微生物组暴露：对儿童过敏性哮喘的影响

• 批准号: 9088338
• 负责人: Christine C Johnson
• 金额: $ 23.2万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9088338
• 关键词: 2 year old; 9 year old; Accounting; Address; Adopted; Affect; Age; Age-Months; Allergens; Allergic; Allergic Disease; Animals; Asthma; Bacteria; Behavior; Biological; Birth; Canis familiaris; Cells; Characteristics; Child; Childhood; Childhood Asthma; Clinical; Cohort Studies; Communities; Data; Data Collection; Development; Disease; Dust; Ecology; Environment; Environmental Exposure; Epidemiologic Studies; Epidemiologist; Equilibrium; Exhibits; Exposure to; Extrinsic asthma; Failure; Family; Feces; Felis catus; Gastrointestinal tract structure; Home environment; House Dust; Household; Housing; Human; Hypersensitivity; IgE; Immune; Immune response; Immune system; Immunoglobulins; Infant; Infant Development; Inflammatory; Inflammatory Bowel Diseases; Instruction; Life; Life Style; Livestock; Measures; Mus; Obesity; Organism; Outcome; Outcome Measure; Ownership; Pattern; Pharmaceutical Preparations; Play; Population Heterogeneity; Program Research Project Grants; Questionnaires; Regulation; Research; Research Design; Research Personnel; Risk; Sampling; Societies; Soil; Stimulus; Supplementation; Taxon; Testing; Work; atopy; cohort; cost; critical period; early life exposure; ethnic diversity; experience; gastrointestinal; gut microbiome; immune function; infancy; interest; microbial; microbial community; microbiome; microbiota; multidisciplinary; new technology; pet animal; population based; protective effect; public health intervention; residence; response; success; theories

PROJECT SUMMARY (See instructions): The overall objective of Project 4 is to assess the relationship between exposure to pets, the infant home and gut microbiomes, and allergic asthma at 9 years of age, using an ethnically diverse, population-based general risk birth cohort (the WHEALS cohort). A premise with growing evidence is that lack of exposure to particular patterns of microbial stimuli during early infancy results in a heightened T-helper (Th) 2 response in the maturing immune system, likely due to a suboptimal regulatory capacity, which in turn is associated in childhood with increased immunoglobulin(lg)E, allergy, and clinical allergic conditions such as asthma. Epidemiological studies have revealed that atopic conditions have increased over the latter half of the twentieth century. Humans in earlier centuries had lifestyles associated with closer direct contact with soil, animals and other humans, suggesting exposure to environments with richer and more diverse microbiological burdens. We hypothesize that evolutionary adaptation to such microbial exposures with respect to immune recognition and regulation may result in untoward consequences when humans are presented with the different, and probably more limited, patterns of microbial exposures found in modern Westernized societies. Our theory is that in many settings, pets, as well as farm animals in close proximity, render the home microbiome, or bacterial community composition (BCC,) to be more similar to early 20th century environments with respect to an increased bacterial richness, diversity and a more even distribution of taxa. This home microbiome impacts directly through effects on the infant gastrointestinal tract BCC the immunogenesis of the infant and subsequently the development of clinically important outcomes such as childhood atopic asthma. Using a new technology (the G3 PhyloChipj, capable of cost-effectively identifying, to a great depth, bacteria in environmental and biological samples, our collaborative team has preliminary data suggesting that the presence of dogs and cats is associated with distinct home and infant gut microbiomes characterized by dramatic increases in bacterial diversity, richness and evenness. Using newly measured outcome variables measured by questionnaire and clinical examinations in the WHEALS cohort, in conjunction with PhyloChip analyses of stored infant stool and dust samples, we will test whether distinct patterns of pet exposure, home microbiome and infant gut microbiome are associated with current allergic asthma at age 9 years.

项目总结（见说明）： 项目4的总体目标是使用一个种族多样的、基于人群的一般风险出生队列（WHEALS队列）评估暴露于宠物、婴儿家中和肠道微生物组与9岁时过敏性哮喘之间的关系。越来越多的证据表明，婴儿早期缺乏特定模式的微生物刺激导致成熟免疫系统中辅助性T细胞（Th）2反应增强，这可能是由于次优调节能力，这反过来又与儿童期免疫球蛋白（Ig）E增加、过敏和临床过敏性疾病（如哮喘）相关。流行病学研究表明，特应性病症在二十世纪后半期有所增加。早几个世纪以来，人类的生活方式与土壤、动物和其他人类有着更密切的直接接触，这表明人类暴露在微生物负荷更丰富、更多样化的环境中。我们假设，进化适应这种微生物暴露方面的免疫识别和调节可能会导致不利的后果时，人类与不同的，可能更有限的，在现代西方社会中发现的微生物暴露模式。我们的理论是，在许多环境中，宠物以及附近的农场动物使家庭微生物组或细菌群落组成（BCC）在增加的细菌丰富度、多样性和更均匀的分类群分布方面更类似于20世纪世纪早期的环境。这种家庭微生物组通过对婴儿胃肠道BCC的影响直接影响婴儿的免疫发生，随后影响临床重要结果的发展，如儿童特应性哮喘。我们的合作团队使用一项新技术（G3 PhyloChipj，能够经济高效地深入识别环境和生物样本中的细菌），初步数据表明狗和猫的存在与不同的家庭和婴儿肠道微生物组有关。细菌多样性、丰富性和均匀性急剧增加。在WHEALS队列中使用通过问卷调查和临床检查测量的新测量的结果变量，结合对储存的婴儿粪便和灰尘样本的PhyloChip分析，我们将测试宠物暴露、家庭微生物组和婴儿肠道微生物组的不同模式是否与9岁时的过敏性哮喘相关。