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: 8662298
• 负责人: THOMAS W FERKOL
• 金额: $ 49.36万
• 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 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8662298
• 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; Massive Parallel Sequencing; 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，以检验新生儿肠道微生物组特征与BPD相关的不良肺部结局相关的假设，包括死亡、技术依赖和需要 36 周和 1 岁时使用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和不患有 BPD 的相关母亲和早产新生儿组之间微生物群组成的差异，2）利用现有数据确定患有和不患有 BPD 的相关母亲和早产新生儿之间肠道微生物群宏基因组和/或转录库的差异。具体目标 II 中确定的与不良肺部结果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，还将为候选基因网络的选择提供信息，这些候选基因网络可以针对该提案的多中心部分进行询问，其中下一代测序将用于确定婴儿和微生物群的等位基因之间的相互作用， 与 BPD 相关的不良肺部结局有关。 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）

项目成果

Normative Left Ventricular M-Mode Echocardiographic Values in Preterm Infants up to 2 kg.

• DOI: 10.1016/j.echo.2017.04.010
• 发表时间: 2017-08
• 期刊: Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
• 作者: Choudhry S;Salter A;Cunningham TW;Levy PT;Nguyen HH;Wallendorf M;Singh GK;Johnson MC
• 通讯作者: Johnson MC

Persistence of right ventricular dysfunction and altered morphometry in asymptomatic preterm Infants through one year of age: Cardiac phenotype of prematurity.

无症状早产儿一岁时右心室功能障碍和形态改变的持续存在：早产儿的心脏表型。

• DOI: 10.1017/s1047951119001161
• 发表时间: 2019
• 期刊: Cardiology in the young
• 影响因子: 1
• 作者: Erickson,CollinT;Patel,MeghnaD;Choudhry,Swati;Bisselou,KarlStessy;Sekarski,Tim;Craft,Mary;Li,Ling;Khuffash,AfifEl;Hamvas,Aaron;Kutty,Shelby;Singh,GautamK;Levy,PhilipT
• 通讯作者: Levy,PhilipT

Effects of frame rate on two-dimensional speckle tracking-derived measurements of myocardial deformation in premature infants.

• DOI: 10.1111/echo.12716
• 发表时间: 2015-05
• 期刊: Echocardiography (Mount Kisco, N.Y.)
• 作者: Sanchez AA;Levy PT;Sekarski TJ;Hamvas A;Holland MR;Singh GK
• 通讯作者: Singh GK

Reference Ranges of Left Ventricular Strain Measures by Two-Dimensional Speckle-Tracking Echocardiography in Children: A Systematic Review and Meta-Analysis.

• DOI: 10.1016/j.echo.2015.11.016
• 发表时间: 2016-03
• 期刊: Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
• 作者: Levy PT;Machefsky A;Sanchez AA;Patel MD;Rogal S;Fowler S;Yaeger L;Hardi A;Holland MR;Hamvas A;Singh GK
• 通讯作者: Singh GK

Sources of methodological variability in phase angles from respiratory inductance plethysmography in preterm infants.

早产儿呼吸电感体积描记法相位角方法变异的来源。

• DOI: 10.1513/annalsats.201310-363oc
• 发表时间: 2014
• 期刊: Annals of the American Thoracic Society
• 影响因子: 8.3
• 作者: Ulm,LaraN;Hamvas,Aaron;Ferkol,ThomasW;Rodriguez,OscarM;Cleveland,ClaudiaM;Linneman,LauraA;Hoffmann,JulieA;Sicard-Su,MariaJ;Kemp,JamesS
• 通讯作者: Kemp,JamesS