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

项目 1 早期微生物群相关危险因素和过敏性哮喘表型多敏高风险的发展

• 批准号: 10480069
• 负责人: Christine C Johnson
• 金额: $ 13.07万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-06 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10480069
• 关键词: 10 year old; 2 year old; Accounting; Address; Adult; Affect; Age; Allergens; Allergic; Allergic Disease; Antibiotics; Asthma; Behavioral; Birth; Breast Feeding; Categories; Characteristics; Child; Childhood; Chronic; Clinical; Collection; Communities; Complex; County; Data; Development; Diagnosis; Diet; Disease; Economics; Electronic Health Record; Environment; Environmental Exposure; Ethnic Origin; Extrinsic asthma; First Pregnancy Trimester; Food; Freezing; Funding; Future; Genetic; Genetic Risk; Health; Health Status; Health system; Home; Hypersensitivity; IgE; Immune; Immune system; Infant; Inhalant dose form; Intervention; Intuition; Late pregnancy; Lead; Life; Longitudinal Studies; Longitudinal cohort study; Marital Status; Mediating; Medicine; Microbe; Mothers; Multivariate Analysis; Mus; Nature; Nested Case-Control Study; Odds Ratio; Outcome; Paper; Pathway interactions; Pattern; Phenotype; Physicians; Pregnancy; Pregnant Women; Prevalence; Preventive; Primary Prevention; Process; Publications; Race; Recording of previous events; Reporting; Research; Research Design; Risk; Risk Factors; Sampling; Serum; Specimen; Subgroup; Techniques; Technology; Time; Vagina; Visit; Work; age group; base; case control; cohort; cost efficient; design; environmental tobacco smoke; epidemiology study; ethnic diversity; falls; gut microbes; gut microbiota; high risk; high risk population; indexing; individualized prevention; infancy; inner city; innovation; maternal microbiota; microbial; microbiota; modifiable risk; offspring; pet animal; prenatal; preventive intervention; pulmonary function; racial and ethnic; recruit; resilience; risk variant; sample collection; sex; social; sociodemographics; stool sample

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.

我们孩子的健康状况对国家具有长期的社会和经济影响。哮喘 是美国儿科年龄组中最常见的慢性病。这种疾病常常会持续到 成年期并与终生肺功能缺陷有关。这些孩子中的大多数也是 过敏，还有一部分患有难以控制的哮喘。尽管付出了大量的研究努力， 过去几十年来，哮喘患病率急剧上升的趋势并未得到缓解。 新的希望集中在调查影响和可能的干预机会的研究上 通过肠道微生物群的研究提供。随着文化独立的出现，这已成为可能 技术。我们最初的 P01 使用我们的 WHEALS 出生队列来证明，许多儿童和 母亲的特征也与婴儿肠道微生物群的组成有关。婴儿 肠道微生物群特征，例如较低的细菌多样性和较高的真菌多样性，是相关的 2 岁时出现多种过敏原致敏 (IgE) 表型，4 岁时出现哮喘。我们的新数据揭示了 这种 2 岁表型与 10 岁时患多敏过敏性哮喘的高风险相关，并且 相同的肠道微生物群特征与这种较高的风险相关。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检查婴儿肠道微生物群与 过敏，或母亲对这种关联的贡献。使用有限的方法获得婴儿粪便样本 机构资金，因此仅在一两个时间点并且相对零星地进行。该项目将 利用基于新的、大型且多样化的卫生系统的一般风险出生队列，重点研究 使用最新的样本采集和分析技术以及粪便样本的采集来了解肠道微生物群 更早和更频繁的婴儿时间点以及妊娠晚期。我们提出了多项详细研究 怀孕期间可能影响母体微生物群的变量，这些影响与孩子的关系如何 过敏致敏的风险，以及母婴肠道微生物群如何调节风险。项目1是 旨在关注母婴暴露和肠道微生物群以及它们与孩子的关系 2 岁时出现高度多重过敏或不过敏（对过敏有抵抗力）的风险。 总而言之，本 P01 中的协调项目正在解决对未来信息丰富的假设 通过行为/社会或直接的方式制定潜在的微生物相关预防干预措施 微生物手段。