The Role of the Microbiome in the Acute Respiratory Distress Syndrome

微生物组在急性呼吸窘迫综合征中的作用

• 批准号: 9013900
• 负责人: Robert Pickett Dickson
• 金额: $ 17.12万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9013900
• 关键词: Adult Respiratory Distress Syndrome; Alveolar; Bacteria; Catecholamines; Cells; Cessation of life; Chronic; Clinical; Clinical Data; Clinical Research; Cohort Studies; Communities; Complement; Complex; Computational Biology; Computer Simulation; Critical Care; Critical Illness; Development; Development Plans; Diagnosis; Disease Progression; Doctor of Philosophy; Early treatment; Ecology; Ensure; Enteral; Enterobacter; Enterobacteriaceae; Epinephrine; Foundations; Functional disorder; Future; Gammaproteobacteria; Gastrointestinal tract structure; Goals; Growth; Human Microbiome; Immigration; Immunology; Inflammation; Inflammation Mediators; Inflammatory; Injury; Interleukin-1 beta; International; Investigation; Knowledge; Logistic Regressions; Lung; Lung diseases; Machine Learning; Mentored Patient-Oriented Research Career Development Award; Mentors; Michigan; Modeling; Morbidity - disease rate; Non-linear Models; Norepinephrine; Pathogenesis; Patients; Physicians; Predisposition; Prevention; Preventive Intervention; Productivity; Pseudomonas; Publishing; Research; Research Methodology; Research Personnel; Research Priority; Risk; Risk Factors; Role; Sampling; Scientist; Sepsis; System; TNF gene; Techniques; Testing; Training; Trauma; United States National Institutes of Health; Universities; Work; career; career development; clinical risk; cytokine; gastrointestinal; gut microbiota; high risk; improved; indexing; member; microbial; microbiome; microbiota; mortality; neutrophil; new therapeutic target; novel; outcome forecast; patient oriented; predictive modeling; prevent; prospective; public health relevance; respiratory; skills; success

 DESCRIPTION (provided by applicant): This K23 proposal will complete Robert Dickson, MD's training towards his long-term career goal of improving our understanding and treatment of lung disease by investigation of the microbiome. Dr. Dickson is a Pulmonary and Critical Care physician and scientist at the University of Michigan with established success in the burgeoning field of lung microbiome studies. This proposal builds on Dr. Dickson's previously acquired expertise in pulmonary pathophysiology and microbial ecology with new training in clinical research methods and computational biology. These established and newly-acquired skills will be integrated to improve our understanding of the role of the microbiome in the pathogenesis of the Acute Respiratory Distress Syndrome (ARDS). This research will be conducted under the guidance of primary mentor Gary B. Huffnagle PhD, co- mentor Theodore J. Standiford MD and an advisory board of accomplished investigators with expertise in clinical research methods, computational biology and lung immunology as well as extensive mentoring success. This 5-year plan includes formal coursework, professional development, and progressively independent research, with defined milestones to ensure productivity and a successful transition to independence. The Acute Respiratory Distress Syndrome (ARDS) is a major cause of morbidity, mortality and expense, responsible for an estimated 74,500 U.S. deaths per year. Numerous studies have identified indirect evidence of translocation of bacteria from the gastrointestinal tract to the lung in patients at risk for ARDS, but to date no study has evaluated the role of microbiome in the pathogenesis of ARDS. This proposal will test the hypothesis that translocation of gut bacteria to the lung provokes the inflammation and injury of ARDS via two specific Scientific Aims. Aim 1 will determine if translocation of enteric bacteria to the lung microbiome precedes the clinical development of ARDS, and Aim 2 will determine the temporal relationship between respiratory dysbiosis, host inflammation and the clinical onset of ARDS. Inherent to completing these high-level aims, Dr. Dickson will execute a prospective cohort study of patients at high risk for ARDS, utilize modern culture-independent techniques of bacterial identification to describe the bacterial communities in the lungs and gastrointestinal tracts of high-risk patients, and apply novel techniques of advanced computational modeling to the complex nonlinear system of ARDS pathogenesis. This work will build to at least two R01 proposals: 1) to determine if the lung microbiome contributes to disease progression among patients with established ARDS and 2) to determine if the lung microbiome can be therapeutically manipulated in critically ill patients to prevent or modulate respiratory disease. n addition to building a foundation for a programmatic line of research to understand the role of the microbiome in lung disease, this proposal will provide Dr. Dickson with research skills applicable to additional domains of human microbiome and ARDS research. This K23 award will equip Dr. Dickson to establish himself as an independent investigator and international leader in this promising field.

 描述（由应用程序提供）：该K23提案将完成医学博士Robert Dickson的培训，以通过调查微生物组来提高我们对肺部疾病的理解和治疗的长期职业目标。 Dickson博士是密歇根大学的肺和重症监护身体和科学家，在肺部微生物组研究的新兴领域取得了成功。该提案建立在迪克森博士先前获得的肺病理生理学和微生物生态学专业知识的基础上，并通过临床研究方法和计算生物学方面的新培训。这些已建立的新获得的技能将集成，以提高我们对微生物组在急性呼吸窘迫综合征（ARDS）发病机理中的作用的理解。这项研究将在主要导师Gary B. Huffnagle博士的指导下进行。这项为期5年的计划包括正式的课程，专业发展和逐步独立的研究，并具有确定的里程碑，以确保生产力和成功过渡到独立性。急性呼吸窘迫综合征（ARDS）是发病率，死亡率和费用的主要原因，估计每年有74,500例美国死亡。大量研究已经确定了细菌从胃肠道易位的间接证据，处于ARDS风险的患者中，但迄今为止，尚未评估任何研究 微生物组在ARD的发病机理中的作用。该提案将检验以下假设：将肠道细菌转移到肺部会通过两个特定的科学目的引起ARD的感染和损伤。 AIM 1将确定肠道细菌向肺微生物组的易位是否在ARDS的临床发展之前，AIM 2将确定呼吸性营养不良，宿主感染和ARDS临床发作之间的临时关系。迪克森博士固有的固有，将对ARDS高风险的患者进行前瞻性队列研究，利用细菌身份的现代与文化无关的技术来描述高风险患者的肺和胃肠道中的细菌群落，并应用高级计算模型的新型非复杂模型系统。这项工作将至少建立两个R01提案：1）确定肺微生物组是否促进了已建立ARDS患者的疾病进展和2））确定是否可以在严重患者的批判性操纵中对肺微生物组进行治疗，以预防呼吸疾病或调节呼吸疾病。 n除了为了解微生物组在肺部疾病中的作用而建立基础，该提案将为迪克森博士提供适用于人类微生物组和ARDS研究的其他领域的研究技能。这项K23奖将使迪克森博士成为这个诺言领域的独立调查员和国际领导人。