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The Neonatal Microbiome and Necrotizing Enterocolitis

新生儿微生物组和坏死性小肠结肠炎

基本信息

批准号：
8318269
负责人：
PHILLIP I TARR
金额：
$ 248.1万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-11 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8318269
关键词：
Abdomen Affect Age Alleles Biological Biomass Birth Caring Case Fatality Rates Child Clinical Clinical Data Clinical Sciences Cohort Studies Collaborations Colon Complication Consensus Databases Development Digestive System Disorders Disease Distal Elderly Enrollment Enteral Epidemiology Feces Functional disorder Genes Genome Human Incidence Inflammatory Inflammatory Bowel Diseases Inflammatory disease of the intestine Informatics Injury Institutes Institution Intestines Left Life Low Birth Weight Infant Lung diseases Microbe Microbiology Necrotizing Enterocolitis Neonatal Neonatal Intensive Care Units Newborn Infant Patients Play Population Populations at Risk Premature Infant Prevention Probiotics Process Relative (related person)Research Research Personnel Resources Risk Risk Factors Role Severities Small Intestines Specimen Staging Stimulus Survivors Testing Time Translational Research Universities Very Low Birth Weight Infant Virus Washington body system cohort density high risk improved insight member microbial microbiome mortality premature prevent response

项目摘要

Necrotizing enterocolitis (NEC) is a devastating disorder that affects approximately 10% of premature infants. Its mortality remains high (15-30%), and its cause remains unknown. About 80% of cases occur within 35 days of birth among hospitalized newborns of low birth weight. Probiotics diminish the incidence and severity of NEC, and NEC does not occur antepartum. NEC affects a readily identifiable at-risk group, has a tightly defined interval before its onset, occurs in an organ system that is intimately associated with a microbial population in flux, has a plausible association with the intestinal microbiota, and cohorts at risk have rarely been studied in large numbers, or prospectively. This disorder, therefore, provides a unique opportunity to explore the role of the human enteric microbiome in a devastating disease. Moreover, NEC epidemiology and age-incidence present an ability to enroll and study cohorts that are highly likely to provide valuable pathophysiologic and microbiologic insights. In this project, we will identify and quantify the microbial components of stool and its products before and at the onset of NEC. In doing so, we will test the overarching hypothesis that NEC is a direct or indirect consequence of the enteric biomass, its products, or both. We will use multicenter cohorts of premature infants at high risk of developing NEC, extend our research on this disease currently sponsored by the Washington University Institute of Clinical and Translational Sciences, and continue our longstanding collaborations with the Genome Center at Washington University and the Washington University Digestive Diseases Research Core Center (Informatics Core). The Aims of this proposal are to (1) conduct a case cohort study in which we compare clinical data and biological specimens from cases and well-matched controls; (2) determine if the kind and density of intestinal biomass, its gene content, and transcriptional activity are associated with, and potential determinants of, NEC; and (3) determine if host risk alleles for intestinal inflammation play a role in the development of NEC. These efforts will be accomplished using subjects from three collaborating neonatal intensive care units (NICUs), focusing on the critical, instructive, and understudied pre-NEC stage of illness, and formulating a data repository that will be a resource for investigators worldwide who wish to focus their efforts on NEC, its precipitants, and its prevention and cure.

坏死性小肠结肠炎（NEC）是一种破坏性疾病，影响约10%的早产儿。它的死亡率仍然很高（15-30%），其原因仍然未知。大约80%的病例发生在35岁以下住院低出生体重新生儿的出生天数。益生菌减少了发病率和严重程度 NEC的，NEC不发生产前。NEC影响一个容易识别的高危人群，在发病前的一段确定的时间内，发生在与微生物密切相关的器官系统中，流动人口，与肠道微生物群有合理的关联，而风险人群很少被大量研究过，或者是前瞻性的。因此，这种疾病提供了一个独特的机会，探索人类肠道微生物组在毁灭性疾病中的作用。此外，NEC流行病学和年龄发病率呈现出招募和研究队列的能力，这些队列极有可能提供有价值的病理生理学和微生物学的见解。在这个项目中，我们将在粪便及其产品的微生物成分之前和之后进行鉴定和量化。 NEC的开始。在此过程中，我们将测试总体假设，即NEC是直接或间接的肠道生物质、其产物或两者的结果。我们将使用多中心队列研究，婴儿在发展NEC的高风险，扩大我们对这种疾病的研究目前赞助的华盛顿大学临床和转化科学研究所，并继续我们的长期与华盛顿大学基因组中心和华盛顿大学消化中心合作疾病研究核心中心（Informatics Core）这项建议的目的是：（1）处理一宗案件一项队列研究，我们比较了病例和匹配良好的病例的临床数据和生物标本（2）测定肠道生物量的种类和密度、基因含量和转录活性与NEC相关，并且是NEC的潜在决定因素;以及（3）确定是否存在肠道感染的宿主风险等位基因。炎症在NEC的发展中起作用。这些工作将使用以下主题完成：三个合作的新生儿重症监护病房（NICU），重点是关键的，指导性的，和研究不足的疾病的NEC前阶段，并制定一个数据库，将成为研究人员的资源世界各地的人希望把他们的努力集中在NEC，其沉淀物，及其预防和治疗。