Disruption of the Microbiome after Severe Traumatic Brain Injury

严重创伤性脑损伤后微生物群的破坏

• 批准号: 9091933
• 负责人: Michael Morowitz
• 金额: $ 23.04万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-12 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9091933
• 关键词: Acute; Admission activity; Adult; Age; Ancillary Study; Antibiotics; Aspirate substance; Asthma; Caring; Cerebrospinal Fluid; Cessation of life; Child; Childhood; Chronic Disease; Chronically Ill; Clinical; Critical Illness; Critically ill children; DNA Sequence; Diabetes Mellitus; Disease; Electronics; Enteral Feeding; Enteral Nutrition; Environment; Feces; Fiber; Foundations; Funding; Future; Health; Human; Human Microbiome; Human body; Immunity; Infection; Infection prevention; Injury; Intervention; Knowledge; Laboratories; Length of Stay; Linear Models; Link; Logistics; Mechanical ventilation; Metabolism; Metadata; Microbe; Modeling; Modification; Monitor; Nervous System Physiology; Neurological outcome; Nosocomial Infections; Observational Study; Oral; Outcome; Outcome Study; Outpatients; Pathologic; Pathway Analysis; Patient Care; Patient risk; Patients; Patients' Rooms; Pattern; Physiology; Pilot Projects; Play; Population; Population Control; Predisposition; Public Health; Research; Ribosomal RNA; Risk; Role; Sample Size; Sampling; Site; Skin; Source; Specificity; Statistical Models; Supplementation; Surface; Swab; Testing; Time; Tongue; Translating; Trauma; Trauma patient; Traumatic Brain Injury; Traumatic injury; United States National Institutes of Health; Vasoconstrictor Agents; Work; adverse outcome; base; cohort; commensal microbes; design; fecal transplantation; gut microbiota; improved; improved outcome; individual patient; microbial; microbiome; microbiota; migration; next generation; novel; nutrition; pathogen; pediatric traumatic brain injury; prospective; public health relevance; study population

 DESCRIPTION (provided by applicant): Bacterial populations associated with the human body play important roles in both health and disease. The objective of this research is to understand how altered patterns of bacterial colonization impact outcomes after major traumatic injury. This proposal is designed as an ancillary study to the ADAPT trial, a NIH-funded observational study of best practices in the care of pediatric traumatic brain injury (TBI). The work is an extension of a pilot study of critically ill children that documented widespread derangements of the microbiome, which in some cases were linked to nosocomial infections. We will use next-generation DNA sequencing to resolve population level bacterial colonization patterns in 50 patients with severe TBI. We will profile colonization patterns using high-throughput 16S rRNA sequencing of stool samples, skin swabs, tongue swabs, tracheal aspirates, and samples of cerebrospinal fluid collected twice weekly after admission to the PICU. A panel of 4 microbiome analyses will be performed to profile the microbiota for each individual patient, and for the entire study population. We will use group-based trajectory analysis to track changes in diversity, presence of dominant nosocomial pathogens, and loss of microbial site-specificity across body sites. Alterations in the microbiota of TBI patients will be compared to colonization patterns in control populations of adults and children (Aim 1). We will use multiple statistical approaches including a hierarchical mixed effect linear model to characterize how the ICU microbiome is impacted by clinical variables, including antibiotic exposure, enteral nutrition, and contamination from the ICU room environment (Aim 2). Finally, we will utilize regression models to test the hypothesis that specific derangements in the microbiome increase the odds of adverse clinical outcomes including nosocomial infection, prolonged hospital stay, death, and poor neurologic function at 6 months (Aim 3). Improved understanding of post-injury colonization patterns could translate to improved outcomes for trauma victims by suggesting more effective patient care strategies, e.g. modification of the microbiome to prevent infection. More broadly, this research will uncover aspects of colonization dynamics with implications for a diverse range of critically ill patients, including both children nd adults.

 描述（由应用提供）：与人体相关的细菌种群在健康和疾病中起重要作用。这项研究的目的是了解细菌定植的模式如何影响重大损伤后的结果。该提案被设计为一项适应试验的辅助研究，这是一项由NIH资助的观察性研究，对小儿创伤性脑损伤（TBI）的最佳实践研究。这项工作是对重症儿童的试点研究的扩展，该研究记录了微生物组的宽度演变，在某些情况下，该研究与医生感染有关。我们将使用下一代DNA测序来解决50例严重TBI患者的种群水平细菌定植模式。我们将使用高通量16S的粪便样品，皮肤拭子，舌头拭子，气管抽吸物和脑脊液的样品进行介绍定植模式，每周两次收集到PICU。将对每个患者以及整个研究人群进行4个微生物组分析小组分析。我们将使用基于组的轨迹分析来跟踪多样性的变化，主导的医院病原体的存在以及整个身体部位的微生物位点特异性的丧失。 TBI患者的微生物群的改变将是 与成人和儿童对照人群中的定殖模式相比（AIM 1）。我们将使用多种统计方法，包括分层混合效应线性模型来表征ICU微生物组如何受到临床变量的影响，包括ICU室环境中的抗生素暴露，肠内营养和污染（AIM 2）。最后，我们将利用回归模型来检验以下假设：微生物组中的特定演变会增加不良临床结果的几率，包括医院感染，长期住院住院，死亡，死亡和6个月的神经系统功能不佳（AIM 3）。通过建议更有效的患者护理策略，例如修饰微生物组以防止感染。更广泛地说，这项研究将发现殖民动态的各个方面，对包括两个孩子和成年人在内的危重患者的潜水员范围都有影响。