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

这项修订后的项目资助(PPG)申请旨在加深对婴儿期接触猫狗与降低过敏性哮喘风险之间的关系的理解。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，即家中宠物的存在会导致家中灰尘的细菌群落组成(BCC)更加多样化，这反过来又会影响住在家里的新生儿肠道BCC的发育。更多样化的肠道BCC改变了婴儿免疫系统的成熟，因此较晚的免疫反应不太可能产生IgE抗体反应和过敏性哮喘。项目1考察了家中猫狗的存在、家中灰尘的bcc、家中婴儿粪便的bcc和过敏之间的关系 2岁时致敏。一种创新的、与培养无关的微阵列(G3 PhyloChip)将被用来利用之前从正在进行的WHEALS出生队列研究中收集的样本来表征BCC。 家庭密件抄送的变化后，引入一只狗也被检查。以进一步研究狗暴露与免疫发育之间的关系。项目2将招募一个新的出生队列，无论有没有养狗，测量婴儿的粪便BCC，并跟踪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使用过敏性哮喘的小鼠模型，进一步检查有狗和没有狗的家里的灰尘对导致肺部炎症的免疫反应的影响。与人类儿童相比，使用小鼠模型可以更详细地研究身体多个区域的免疫功能。项目4再次利用现有的WHEALS出生队列来检查狗或猫在一岁时暴露于猫狗、6个月婴儿大便BCC与过敏性哮喘的存在之间的关系。 9岁。这些项目得到五个核心的支持，每个核心都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.