Influence of the Enteric Microbiome on the Genesis of Bronchopulmonary Dysplasia

描述(申请人提供)：支气管肺发育不良(BPD)是早产后肺部发育障碍的结果，导致终生肺部疾病。宫内和出生后的肺部炎症有助于BPD的关键组成部分--呼吸道结构的简化和肺血管阻力的增加。人类微生物组项目旨在了解寄主中的微生物群落与寄主本身之间的相互作用。新出现的数据表明，胃肠道共生生物成分之间的失衡与特应性、过敏性鼻炎或反复喘息有关。这些数据促使人们考虑肠道微生物区系介导的肺部炎症作为BPD的触发因素的作用。在这个单一中心的项目中，有限的多导睡眠图和超声心动图将被用来非侵入性地和纵向地评估早产儿的空间和肺血管发育，这些早产儿有患BPD的风险&30周，以检验新生儿肠道微生物群的特征与BPD相关的不良肺部结果相关的假设，包括死亡，技术依赖，以及在36周和1岁时需要支气管扩张剂或皮质类固醇。华盛顿大学正在进行的以早产儿肠道微生物群为特征的平行倡议将被用来探索这种生物量与BPD相关不良肺部结局的发展之间的联系。具体目标是：1)利用现有数据确定患有和不患有BPD的连锁母亲和早产儿群体之间的微生物区系组成的差异，以及2)利用现有数据确定连锁母亲和患有BPD和不患有BPD的早产儿之间肠道微生物区系的元基因组和/或转录谱系的差异。在特定目标II中确定的与肺不良结局相关的元基因组和转录差异将允许识别适合于早期干预和预防BPD的因素，此外，还将为选择候选基因网络提供信息，这些候选基因网络可以被询问这项建议的多中心组成部分，其中将使用下一代测序来识别与BPD相关的不良肺结局相关的婴儿和微生物群的等位基因之间的相互作用。 相关性(见说明书)：拟议的研究将评估早产儿肠道中的细菌是否在支气管肺发育不良的发展中发挥作用，支气管肺发育不良是早产儿最严重的慢性肺部问题。确定这些细菌所起的作用将使早期治疗成为可能，以努力防止这些肺部问题的发展。(摘要结束)

DESCRIPTION (provided by applicant): Bronchopulmonary dysplasia (BPD) results from disrupted lung development after premature birth and results in life long pulmonary morbidity. Intrauterine and postnatal lung inflammation contribute to structural airway simplification and increased pulmonary vascular resistance, critical components of BPD. The Human Microbiome Project is designed to understand the interactions between microbial communities that inhabit a host and the host itself. Emerging data suggest that imbalances between components of commensal organisms in the gastrointestinal tract are associated with atopy, allergic rhinitis, or recurrent wheezing. These data prompt consideration of the role for gut microbiota-mediated lung inflammation as a trigger for BPD. In this single center project, limited polysomnography and echocardiography will be used to non- invasively and longitudinally assess airspace and pulmonary vascular development in premature newborns < 30 weeks' gestation who are at risk for developing BPD to test the hypothesis that signatures of the neonatal enteric microbiome are associated with BPD-related adverse pulmonary outcomes, including death, technology dependence, and need for bronchodilators or corticosteroids at 36 weeks and 1 year of age. Ongoing, parallel initiatives at Washington University that are characterizing the enteric microbiome of premature newborns will be leveraged to explore associations between this biomass and the development of BPD-related adverse pulmonary outcomes. The Specific Aims are: 1) utilize existing data to determine differences in the composition of the microbiota between groups of linked mothers and premature newborns with and without BPD, and 2) utilize existing data to determine differences in the metagenomic and/or transcriptional repertoire of the enteric microbiota between linked mothers and premature newborns with and without BPD. The metagenomic and transcriptional differences identified in Specific Aim II that are associated with adverse pulmonary outcomes will permit identification of factors that are amenable to early intervention and prevention of BPD, and furthermore, will inform selection of candidate gene networks that can be interrogated for the multicenter component of this proposal in which next generation sequencing will be used to identify the interactions between and among alleles of the infant and microbiota that are associated with BPD-related adverse pulmonary outcomes. RELEVANCE (See instructions): The proposed studies will evaluate whether bacteria in the intestinal tract of premature newborns play a role in the development of bronchopulmonary dysplasia, the most significant chronic lung problem of prematurity. Identifying the role that these bacteria play will permit early treatment in an effort to prevent the development of these lung problems. (End of Abstract)