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

项目总结(见说明)： 项目4的总体目标是使用种族多样化、基于人群的一般风险出生队列(WHEALS队列)，评估暴露于宠物、婴儿家庭和肠道微生物群与9岁过敏性哮喘之间的关系。一个有越来越多证据的前提是，在婴儿早期缺乏接触特定模式的微生物刺激会导致成熟免疫系统中T辅助细胞(Th)2反应增强，这可能是由于调节能力不佳，而这反过来又与童年时免疫球蛋白(Lg)E增加、过敏和临床过敏情况(如哮喘)有关。流行病学研究表明，在二十世纪后半叶，特应性疾病有所增加。在更早的几个世纪里，人类的生活方式与土壤、动物和其他人类的直接接触更密切相关，这表明人类暴露在微生物负担更丰富、更多样化的环境中。我们假设，当人类面临现代西化社会中发现的不同的、可能更有限的微生物暴露模式时，在免疫识别和调节方面对这种微生物暴露的进化适应可能会导致不良后果。我们的理论是，在许多环境中，宠物以及邻近的农场动物使家庭微生物群或细菌群落组成(BCC)在细菌丰富度、多样性和分类群分布更均匀方面更类似于20世纪初的环境。这种家庭微生物群通过对婴儿胃肠道、BCC、婴儿的免疫发生以及随后临床上重要结果的发展，如儿童特应性哮喘的影响而直接影响。利用一种新技术(G3 PhyloChipj)，能够经济高效地深入识别环境和生物样本中的细菌，我们的合作团队拥有初步数据，表明猫狗的存在与不同的家庭和婴儿肠道微生物群有关，其特征是细菌多样性、丰富度和均衡度大幅增加。使用WHEALS队列中通过问卷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，我们将测试不同模式的宠物暴露、家庭微生物群和婴儿肠道微生物群是否与9岁时当前的过敏性哮喘有关。

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.