Influence of the Enteric Microbiome on the Genesis of Bronchopulmonary Dysplasia

肠道微生物组对支气管肺发育不良发生的影响

• 批准号: 8464209
• 负责人: THOMAS W FERKOL
• 金额: $ 46.94万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8464209
• 关键词: 1 year old; Adrenal Cortex Hormones; Alleles; Allergic rhinitis; Bacteria; Biomass; Blood Vessels; Bronchodilator Agents; Bronchopulmonary Dysplasia; Candidate Disease Gene; Cessation of life; Chronic; Clinical Research; DNA; Data; Dependence; Development; Early Intervention; Early treatment; Echocardiography; Enteral; Gastrointestinal tract structure; Genes; Genome; Human Microbiome; Infant; Instruction; Intervention; Intestines; Life; Link; Lung; Lung Inflammation; Measures; Mediating; Messenger RNA; Metagenomics; Morbidity - disease rate; Mothers; Necrotizing Enterocolitis; Neonatal; Newborn Infant; Organism; Outcome; Pathogenesis; Play; Polysomnography; Pregnancy; Premature Birth; Prevention; Pulmonary Vascular Resistance; Pulmonary function tests; Recurrence; Research; Research Proposals; Risk; Role; Sampling; Severities; Shotgun Sequencing; Specimen; Technology; Testing; Time; Transcript; Universities; Washington; Wheezing; abstracting; adverse outcome; atopy; design; gut microbiota; lung development; member; microbial; microbial community; microbiome; next generation sequencing; postnatal; premature; prevent

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)

描述（由申请人提供）：支气管肺发育不良（BPD）是由早产后肺部发育受损引起的，并导致终生肺部发病。宫内和产后肺部炎症导致气道结构简化和肺血管阻力增加，这是 BPD 的关键组成部分。人类微生物组项目旨在了解宿主微生物群落与宿主本身之间的相互作用。新数据表明，胃肠道共生生物成分之间的不平衡与特应性、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介导的肺部炎症作为 BPD 触发因素的作用。在这个单中心项目中，有限的多导睡眠图和超声心动图将用于非侵入性和纵向评估妊娠<30周的早产儿的空腔和肺血管发育，这些早产儿有发生BPD的风险，以检验新生儿肠道特征的假设微生物组与 BPD 相关的不良肺部结局相关，包括死亡、技术依赖以及 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、描述早产儿肠道微生物组特征的并行举措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关联。具体目标是：1) 利用现有数据确定患有或不患有 BPD 的母亲和早产儿之间微生物群组成的差异，2) 利用现有数据确定宏基因组和/或转录库的差异患有或不患有 BPD 的母亲和早产儿之间的肠道微生物群。具体目标 II 中确定的与不良肺部结局相关的宏基因组和转录差异将允许识别适合早期干预和预防 BPD 的因素，此外，还将为选择可用于多中心研究的候选基因网络提供信息。该提案的组成部分，其中下一代测序将用于识别与 BPD 相关的不良肺部结果相关的婴儿等位基因和微生物群之间的相互作用。 相关性（参见说明）：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（早产儿最重要的慢性肺部问题）的发展中发挥作用。确定这些细菌所起的作用将有助于早期治疗，以防止这些肺部问题的发展。 （摘要完）