Pets and the Infant Microbiome: Effect on Immune Maturation & Atopic Asthma

这项修订后的计划项目资助（PPG）申请旨在加深对婴儿期狗或猫暴露与降低过敏性哮喘风险之间关系的理解。我们认为，这种保护性关联与免疫发育过程中微生物刺激的不同模式有关。 四个协同项目将检验我们的假设，即家中宠物的存在导致家中灰尘的细菌群落组成（BCC）更加多样化，这反过来又会影响家中新生儿肠道BCC的发展。更多样化的肠道BCC改变了婴儿免疫系统的成熟，使得后来的免疫应答不太可能产生IgE抗体应答和过敏性哮喘。项目1研究了家中狗或猫的存在、家中灰尘的BCC、家中婴儿粪便的BCC与过敏性疾病之间的关系。 在2岁时致敏。一种创新的，不依赖于培养的微阵列（G3 PhyloChip）将被用来表征BCC，利用以前从正在进行的WHEALS出生队列研究中收集的样本。 家庭BCC的变化后，引入一只狗也进行了检查。进一步研究犬暴露与免疫发育之间的关系。项目2将招募一个新出生的儿童队列，无论是否与狗一起生活，测量婴儿粪便BCC，并对该队列进行详细的免疫功能研究，直到18个月大，以确定狗暴露对免疫成熟的影响。项目3使用过敏性哮喘小鼠模型，进一步研究来自有狗和没有狗的家庭的房屋灰尘对导致肺部炎症的免疫反应的影响。使用小鼠模型可以比人类儿童更详细地研究身体多个隔室的免疫功能。项目4再次利用现有的WHEALS出生队列研究了1岁时狗或猫暴露、6个月婴儿粪便BCC和12岁时过敏性哮喘存在之间的关系。 九岁。这些项目由五个核心项目支持，每个核心项目为所有四个项目提供基本服务。

This revised Program Project Grant (PPG) application seeks an increased understanding of the relationships between dog or cat exposure during infancy and a lower risk of allergic asthma. We believe that this protective association is related to different patterns of microbial stimulation during immune development. Four synergistic Projects will examine our hypothesis that the presence of pets in a home results in a more diverse bacterial community composition (BCC) of the dust in the home which in turn influences the development of the gut BCC of a newborn infant living in the home. A more diverse gut BCC shifts the maturation of the infant's immune system such that later immune responses are less likely to produce IgE antibody responses and allergic asthma. Project 1 examines the relationships between the presence of a dog or cat in a home, the BCC of dust in the home, the BCC of stools of infants living in homes and allergic sensitization at 2 years of age. An innovative, culture-independent microarray (G3 PhyloChip) will be used to characterize the BCCs utilizing previously collected samples from the ongoing WHEALS birth cohort study. Changes in home BCC following introduction of a dog are also examined. To further examine relationships between dog exposure and immune development. Project 2 will recruit a new birth cohort of children either living with or without a dog, measure infant stool BCC, and follow the cohort with detailed studies of immune function until 18 months of age to determine the impact of dog exposure on immune maturation. Project 3 uses mouse models of allergic asthma to further examine the influence of house dust from homes with and without dogs on immune responses that result in lung inflammation. The use of mouse models allows more detailed studies of immune functions from multiple compartments of the body than are possible with human children. Project 4 again utilizes the existing WHEALS birth cohort to examine the relationships between dog or cat exposure during the first year of age, 6-month infant stool BCC, and the presence of allergic asthma at 9 years of age. The Projects are supported by five Cores which each provide essential services to all four Projects.