Binational Early Asthma & Microbiome Study (BEAMS)

梁摘要：总体 在过去的几十年里，儿童哮喘的患病率显著增加，这是一个潜在的解释 这一热潮是由于卫生条件的改善而减少了对保护性环境微生物的接触 以及在怀孕期间和生命早期使用/过度使用抗微生物产品。为了支持这一论点，有几个 在与世隔绝的农村社区进行的研究报告称，动物儿童的哮喘患病率较低 农民比他们的非农民同龄人更严重地暴露在环境微生物中。如果这些 观察结果是否适用于更多的美国主流人群尚不清楚。我们最近观察到墨西哥人 居住在亚利桑那州图森市的美国儿童儿童哮喘患病率是 在墨西哥的诺加利斯。哮喘发病率的巨大差异表明，即使在这个有限的地理区域 地区和祖先相似的人群中，可能存在不同的暴露，这解释了相对的 墨西哥针对哮喘的保护措施。图森位于墨西哥诺加莱斯以北70英里处，该市有20万居民 这座城市位于美墨边境的南面。墨西哥的诺加莱斯缺乏公共卫生设施和贫困 房价非常高。在初步数据中，我们观察到存在于 灰尘、饮用水和两个城市之间一个月大的儿童的粪便中。基于这些发现， 我们提出了两国早期哮喘和微生物组研究(BEMS)。BEAM的总体目标是： 识别与哮喘保护相关的不同的早期生命微生物和免疫发育轨迹 在墨西哥的诺加莱斯与亚利桑那州的图森市进行比较，以及促进他们的环境因素； 提供这种保护的特定微生物、基因及其产物；并通过以下方式确定其机制 这些微生物群落或他们的产品可以促进哮喘保护。为了实现这些目标， Beans将有三个项目和四个核心。我们将招收250名墨西哥怀孕的母亲/子女 每个城市的祖先。我们将彻底评估环境微生物暴露、产妇肠道微生物区系和 微生物基因表达、母体免疫标志物和胎粪微生物群。我们将把这些联系起来 儿童早期粪便微生物组和代谢组特征及哮喘相关免疫标志物 孩子的血液，通过质量细胞仪分析和单细胞表观遗传和基因表达进行评估 研究，以及2岁以前哮喘相关的临床表型。我们还将在小鼠模型中评估 解释其对儿童哮喘发展保护作用的特定分子机制 存在于墨西哥诺加莱斯的特定微生物菌株和代谢物。我们期待BEAM能提供更好的 了解哮喘的早期起源和适用于墨西哥的新哮喘预防策略- 美国人，可能对所有美国人也是如此。

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.