Binational Early Asthma & Microbiome Study (BEAMS)

两国早期哮喘

基本信息

批准号：
10214518
负责人：
Susan Veronica Lynch
金额：
$ 303.59万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-10 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10214518
关键词：
2 year old Adult Air Allergic American Amish Animal Model Animals Area Arizona Asthma Biological Markers Birth Blood Border Community Cells Characteristics Child Childhood Childhood Asthma Cities Clinical Cytometry Data Development Dust Enrollment Environment Environmental Exposure Environmental Risk Factor Eosinophilia Epidemiology Epigenetic Process Ethnic group Exposure to Farming environment Feces Future Gene Expression Genes Genetic Genomics Geographic Locations Germ-Free Goals Health Home Hospitalization Human Human Microbiome Hypersensitivity Immune Immune response Immunity Immunologic Markers Immunologics Immunology Infant Intervention Lactobacillus Length Life Longitudinal cohort Low Prevalence Mainstreaming Meconium Metabolic Mexican Mexican Americans Mexico Microbe Modeling Modification Molecular Mothers Mus Natural experiment Not Hispanic or Latino Outcome Pathway interactions Pattern Population Poverty Pregnancy Pregnant Women Prevalence Prevention strategy Primary Prevention Productivity Program Research Project Grants Reporting Risk Rural Community Sampling Sanitation Scientist Series Side Statistical Methods Time United States Wheezing analytical method antimicrobial asthma model asthma prevention base clinical phenotype drinking water experience experimental study farmer fecal metabolome fecal microbiome gene product gut microbiome gut microbiota hutterite immune function infant gut microbiome innovation maternal microbiome microbial microbial community microbiome microbiome research microbiota mouse model offspring peer prevent protective effect recruit

2 year old Adult Air Allergic American Amish Animal Model Animals Area Arizona Asthma Biological Markers Birth Blood Border Community Cells Characteristics Child Childhood Childhood Asthma Cities Clinical Cytometry Data Development Dust Enrollment Environment Environmental Exposure Environmental Risk Factor Eosinophilia Epidemiology Epigenetic Process Ethnic group Exposure to Farming environment Feces Future Gene Expression Genes Genetic Genomics Geographic Locations Germ-Free Goals Health Home Hospitalization Human Human Microbiome Hypersensitivity Immune Immune response Immunity Immunologic Markers Immunologics Immunology Infant Intervention Lactobacillus Length Life Longitudinal cohort Low Prevalence Mainstreaming Meconium Metabolic Mexican Mexican Americans Mexico Microbe Modeling Modification Molecular Mothers Mus Natural experiment Not Hispanic or Latino Outcome Pathway interactions Pattern Population Poverty Pregnancy Pregnant Women Prevalence Prevention strategy Primary Prevention Productivity Program Research Project Grants Reporting Risk Rural Community Sampling Sanitation Scientist Series Side Statistical Methods Time United States Wheezing analytical method antimicrobial asthma model asthma prevention base clinical phenotype drinking water experience experimental study farmer fecal metabolome fecal microbiome gene product gut microbiome gut microbiota hutterite immune function infant gut microbiome innovation maternal microbiome microbial microbial community microbiome microbiome research microbiota mouse model offspring peer prevent protective effect recruit

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项目摘要

BEAMS ABSTRACT: Overall Prevalence of childhood asthma has significantly increased in the last decades, and one potential explanation for this upsurge is decreased exposure to protective environmental microbes due to improvements in sanitation and use/overuse of antimicrobial products during pregnancy and early life. In support of this contention, several studies in isolated rural communities have reported lower prevalence of asthma among children of animal farmers more heavily exposed to environmental microbes than among their non-farmer peers. If these observations are applicable to more mainstream US populations is unknown. We recently observed that Mexican American children living in Tucson, Arizona have a prevalence of childhood asthma that is fourfold higher than in Nogales, Mexico. This dramatic difference in rates of asthma suggests that, even in this limited geographic region and among an ancestrally similar population, differential exposures may exist which account for relative protection against asthma in Mexico. Tucson is only 70 miles north of Nogales, Mexico, which is a 200k inhabitant city located just south of the US-Mexico border. Nogales, Mexico lacks public sanitation facilities and poverty rates are very high. In preliminary data, we observed marked differences in microbial communities present in dust, drinking water, and in stools of one-month-old children between the two cities. Based on these findings, we propose the Binational Early Asthma and Microbiome Study (BEAMS). The BEAMS overall goals are: to identify divergent early-life microbial and immune developmental trajectories associated with asthma protection in Nogales, Mexico compared with Tucson, Arizona, and the environmental factors that promote them; to isolate the specific microbes, genes and their products that confer such protection; and to ascertain the mechanisms by which these microbial communities or their products promote asthma protection. To accomplish these goals, BEAMS will have three Projects and four Cores. We will enroll 250 pregnant mother/offspring dyads of Mexican ancestry in each city. We will thoroughly assess environmental microbial exposure, maternal gut microbiota and microbial gene expression, maternal immune markers and meconium microbiome. We will relate these characteristics to child’s fecal microbiome and metabolome in early life, to asthma-related immune markers in the child’s blood, as assessed by mass cytometry analysis and single cell epigenetic and gene expression studies, and to asthma-related clinical phenotypes by age 2 years. We will also assess in mouse models the specific molecular mechanism that explain the protective effects against the development of childhood asthma of specific microbial strains and metabolites present in Nogales, Mexico. We expect BEAMS to offer a better understanding of the early origins of asthma and new asthma prevention strategies applicable to Mexican- Americans, and potentially to all Americans.

横梁摘要：总体在过去的几十年中，儿童哮喘的患病率显着增加，有一个潜在的解释因为这种情况的高潮是由于卫生条件的改善而降低了保护环境微生物的暴露并在怀孕和早期使用/过度使用/过度使用抗菌产品。为了支持这个内容，有几个在孤立的农村社区中的研究报告说，动物儿童的哮喘患病率较低与非农民同龄人相比，农民暴露于环境微生物。如果这些观察结果适用于更多主流美国人群。我们最近观察到墨西哥居住在亚利桑那州图森的美国儿童的儿童哮喘患病率比在墨西哥的诺加莱斯。这种哮喘率的巨大差异表明，即使在这个有限的地理上地区和祖先相似的人口中，可能存在差异暴露，这是相对的保护墨西哥哮喘。图森（Tucson）在墨西哥诺加莱斯（Nogales）以北70英里处，这是200k的影响力城市位于美墨边境南部。墨西哥Nogales缺乏公共卫生设施和贫困费率很高。在初步数据中，我们观察到存在于两个城市之间的一个月大儿童的粪便，饮用水和凳子。基于这些发现，我们提出了双性化早期哮喘和微生物组研究（梁）。梁的总体目标是：确定与哮喘保护相关的早期生命微生物和免疫发育轨迹与图森，亚利桑那州的Nogales，墨西哥和促进它们的环境因素相比；分离特定的微生物，基因及其产品会导致这样的保护；并通过这些微生物群落或其产品促进了哮喘保护。为了实现这些目标，梁将有三个项目和四个核心。我们将注册墨西哥250个怀孕的母亲/后代二元每个城市的祖先。我们将彻底评估环境微生物的暴露，母体肠道微生物群和微生物基因表达，母体免疫标记和胎粪微生物组。我们将与这些联系早期儿童粪便微生物组和代谢组的特征，与哮喘相关的免疫标记通过质量细胞仪分析以及单细胞表观遗传和基因表达评估，孩子的血液研究，以及2岁年龄段的与哮喘相关的临床表型。我们还将在鼠标模型中评估特定的分子机制，解释了对儿童哮喘发展的受保护作用墨西哥Nogales中存在的特定微生物菌株和代谢产物。我们希望横梁能提供更好的了解适用于墨西哥的哮喘和新的预防哮喘策略的早期起源美国人，有可能对所有美国人。