Evaluation of Soluble Fiber as a Strategy to Decrease Asthma Morbidity in Underserved Populations

项目摘要 大约7.7%的美国人口患有哮喘，并且自20世纪80年代以来发病率一直在增加。在 亚利桑那州，哮喘患病率超过全国平均水平，大多数哮喘诊断是在 凤凰城都会区。遗传风险因素已被确定在哮喘。然而，稳定 美国人群中哮喘患病率的增加表明，环境暴露或其他 肺外因素，如饮食和肠道微生物群，可能在哮喘的发展中起关键作用。 哮喘患病率和发病率的健康差异在来自低收入城市的个体中突出显示， 营养健康差异更有可能存在的地区。例如，贫困城市住宅是一个 报告哮喘发作的个体风险因素，以及哮喘相关访视的几率更高 急诊科少数群体儿童受社会经济地位低下的影响特别大。一 最近的一项研究表明，31.4%的非西班牙裔黑人儿童和25.2%的西班牙裔儿童生活在 而非西班牙裔白色儿童的贫困率为9.4%。经济上处于不利地位 城市人口还经历着营养健康的差距，包括低纤维饮食，这导致了 肠道微生物组，并可能解释哮喘风险的差异。膳食纤维是复杂的碳水化合物， 抵抗宿主酶在小肠中的代谢，并在结肠中由常驻微生物发酵。 可溶性纤维的肠道微生物发酵导致代谢副产物的产生，例如短纤维素。 链脂肪酸（SCFAs）乙酸酯、丙酸酯和丁酸酯，它们是起连接作用的重要分子 微生物和宿主免疫系统之间的联系我们假设低纤维饮食是一个关键，但 研究不足，哮喘健康差异的因素。本提案的总体目标是确定 肠道微生物组修饰剂（纤维）对服务不足人群中微生物组成和功能的影响。在 此外，我们还将通过以下方法确定补充可溶性纤维在减轻气道炎症中的作用： 肠道微生物组-气道轴。这一建议的假设是，肠道微生物代谢的饮食 纤维与SCFA的结合将通过改变T细胞和嗜酸性粒细胞的表型来减少气道炎症。我们有 组建了一支强大的临床医生和科学家团队，我们利用我们的纤维干预试点研究， 儿童哮喘队列达到3个目标。首先，我们会透过公众健康委员会，加强社区伙伴关系 移动的哮喘诊所（Breath移动的）评估基线纤维消耗和肠道微生物群， 在马洛卡县服务不足的社区。其次，我们将评估可溶性纤维的效果 补充剂在儿童哮喘队列中的应用。最后，我们将评估微生物来源的SCFAs对关键 免疫细胞群体。这些目标的完成将提供可以指导公共卫生的证据 在低社会经济地位人群中进行营养干预，以改善哮喘结局并促进健康公平。

PROJECT SUMMARY Approximately 7.7% of the US population have asthma, and incidence has been increasing since the 1980s. In Arizona, asthma prevalence exceeds the national average, with the majority of asthma diagnoses made in the Phoenix Metropolitan Area. Genetic risk factors have been identified in asthmatics. However, the steady increase in the prevalence of asthma in the US population suggests that environmental exposures or other extrapulmonary factors, such as diet and the gut microbiota, may play a critical role in asthma development. Health disparities in asthma prevalence and morbidity are highlighted in individuals from low-income urban areas where nutritional health disparities are more likely to exist. For example, poor-urban residence is an individual risk factor for reporting an asthma attack and having higher odds for an asthma-related visit to the Emergency Department. Minority children are disproportionately affected by low socioeconomic status. A recent study demonstrated that 31.4% of non-Hispanic Black children, and 25.2% of Hispanic children lived under the poverty threshold compared to 9.4% non-Hispanic white children. Economically disadvantaged urban populations also experience a nutritional health disparity, including a low fiber diet that leads to shifts in the gut microbiome and may explain differences in asthma risk. Dietary fibers are complex carbohydrates that resist metabolism in the small intestine by host enzymes and are fermented in the colon by resident microbes. Gut microbial fermentation of soluble fibers results in production of metabolic by-products such as the short chain fatty acids (SCFAs) acetate, propionate, and butyrate, which are important molecules that act as a link between the microbiota and host immune system. We hypothesize that a low fiber diet is a critical, but understudied, factor in asthma health disparities. The overall goals of this proposal are to determine the effect of a gut microbiome modifier (fiber) on microbial composition and function in an underserved population. In addition, we will determine the effect of soluble fiber supplementation in reducing airway inflammation via the gut microbiome-airway axis. The hypothesis governing this proposal is that gut microbial metabolism of dietary fiber to SCFAs will reduce airway inflammation by altering the phenotype of T cells and eosinophils. We have assembled a strong team of clinicians and scientists, and we draw on our pilot study of fiber intervention in a pediatric asthma cohort to achieve 3 aims. First, we will build on the community partnerships through the PCH Mobile Asthma Clinic (Breathmobile) to assess baseline fiber consumption and gut microbiota across underserved communities in Maricopa County. Second, we will evaluate the effect of a soluble fiber supplement in a pediatric asthma cohort. Finally, we will evaluate the effect of microbial-derived SCFAs on key immune cell populations. Completion of these aims will provide evidence that can guide public health nutritional interventions in low SES populations to improve asthma outcomes and advance health equity.