Project 1 Early Microbiota-Related Risk Factors and the Development of a Multi-Sensitized High Risk for Allergic Asthma Phenotype

我国儿童的健康状况对国家具有长期的社会和经济影响。哮喘 是美国儿童年龄组中最常见的慢性疾病。这种疾病往往会持续到 成年期，并与肺功能的终身缺陷有关。这些孩子中的大多数也是 过敏性疾病，还有一个亚组患有难以控制的哮喘。尽管有大量的研究工作， 过去几十年来哮喘发病率的急剧增加并没有得到缓解。 新希望的研究重点是调查影响和可能的干预机会 通过对肠道微生物群的研究。随着独立于文化的 技术.我们最初的P01使用我们的WHEALS出生队列来证明， 母亲的特征也与婴儿的肠道微生物群组成有关。婴儿 肠道微生物群特征，如较低的细菌多样性和较高的真菌多样性， 2岁时为多变应原致敏（IgE）表型，4岁时为哮喘。 2岁时的表型与10岁时多发致敏过敏性哮喘的高风险相关， 相同的肠道微生物群特征与这种更高的风险相关。我们新的P01小鼠数据支持 母体微生物群对后代免疫系统的影响。 WHEALS出生队列最初并不是为了研究婴儿肠道微生物群与 过敏，或者母亲对这种联系的贡献。婴儿粪便样本是用有限的 机构基金，因此只有一个或两个时间点和相对零星。该项目将 利用一个新的，大的和多样化的卫生系统为基础的一般风险出生队列，重点是研究 利用最新的样本收集和分析技术以及粪便标本的收集， 更早和更频繁的婴儿时间点和一个在怀孕后期。我们建议详细研究多种 怀孕期间可能影响母体微生物群的变量，这些影响如何与孩子的 过敏致敏的风险，以及母婴肠道微生物如何介导风险。项目1是 旨在了解母婴接触和肠道微生物以及它们如何与儿童的 在2岁时有高度多致敏或不致敏（对致敏有恢复力）的风险。 总之，本P01中的协调项目正在解决对未来非常有用的假设 开发潜在的微生物相关预防干预措施，通过行为/社会或直接 微生物手段

The health status of our children has long lasting social and economic ramifications for the nation. Asthma is the most common chronic condition in the U.S. pediatric age group. This disease often carries on into adulthood and is associated with lifelong deficits in lung function. The majority of these children are also allergic, and a sub-group have asthma that is difficult to control. Despite substantial research effort, the dramatic increase in asthma prevalence over the past decades has not been mitigated. New hope is centered on research investigating the influence and possible interventional opportunities afforded by study of the gut microbiota. This has become possible with the advent of culture-independent technology. Our initial P01 used our WHEALS birth cohort to demonstrate that numerous child and also maternal characteristics were associated with the infant's gut microbiota community composition. Infant gut microbiota characteristics, such as lower bacterial diversity and higher fungal diversity, were associated with a multi-allergen-sensitized (IgE) phenotype at age 2 years and asthma at age 4 yrs. Our new data reveals that this age 2yr phenotype is associated with a high risk of multi-sensitized allergic asthma at age 10 yrs, and the same gut microbiota characteristics are associated with this higher risk. Our new P01 murine data supports a maternal microbiota influence on the offspring's immune system. The WHEALS birth cohort was not initially designed to examine how the infant gut microbiota is related to allergy, or the maternal contributions to this association. Infant stool samples were obtained using limited institutional funds and therefore at only one or two points in time and relatively sporadically. This Project will capitalize on a new, large and diverse health system-based general risk birth cohort with the focus of studying the gut microbiota with the latest sample collection and analytic techniques and collection of stool specimens at earlier and more frequent infant time points and one in late pregnancy. We propose detailed studies of multiple variables likely to affect the maternal microbiota during pregnancy, how these effects are related to the child's risk of allergic sensitization, and how the maternal and infant gut microbiotas can mediate risk. Project 1 is designed to home in on maternal/infant exposures and gut microbiotas and how they associate with the child's risk of becoming highly multi-sensitized or not sensitized (resilient to sensitization) by the age of 2 yrs. Altogether, the coordinated Projects in this P01 are addressing hypotheses highly informative to future development of potential microbial-related preventive interventions through both behavioral/social or direct microbial means.