The Neonatal Microbiome and Necrotizing Enterocolitis

新生儿微生物组和坏死性小肠结肠炎

• 批准号: 8134250
• 负责人: PHILLIP I TARR
• 金额: $ 262.18万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-11 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8134250
• 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

DESCRIPTION: 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.

描述：坏死性小肠结肠炎（NEC）是一种毁灭性疾病，影响了大约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％的病例发生在出生后出生后35天内的低出生体重。益生菌减少了NEC的发病率和严重程度，并且NEC不会发生。 NEC会影响一个易于识别的处于危险组，在发作之前具有紧密定义的间隔，发生在与通量中的微生物人群密切相关的器官系统中，与肠道微生物群具有合理的关联，并且在风险中很少进行大量研究或前瞻性研究。因此，这种疾病为探索人类肠微生物组在毁灭性疾病中的作用提供了独特的机会。此外，NEC的流行病学和年龄段具有入学和研究队列的能力，这些能力极有可能提供有价值的病理生理和微生物学洞察力。 在该项目中，我们将在NEC开始之前和处确定并量化粪便及其产品的微生物成分。通过这样做，我们将检验总体假设，即NEC是肠生物质，其产品或两者兼而有之的直接或间接结果。我们将使用具有发展NEC高风险的早产婴儿的多中心队列，扩展了有关华盛顿大学临床和转化科学研究所目前赞助的该疾病的研究，并继续与华盛顿大学基因组中心和华盛顿大学消化疾病消化疾病研究中心（Informatics Core Core）继续我们的长期合作。该提案的目的是（1）进行一项案例队列研究，在该研究中，我们比较了病例和匹配良好的对照的临床数据和生物标本； （2）确定NEC的肠生物量，其基因含量和转录活性的种类和密度是否与NEC的潜在决定因素相关； （3）确定肠道炎症的宿主风险等位基因是否在NEC的发展中起作用。这些努力将使用来自三个合作的新生儿重症监护病房（NICUS）的主题来完成，重点关注关键，启发性和研究的疾病前疾病前阶段，并制定一个数据存储库，这将成为全球研究人员的资源，他们希望将精力集中在NEC，其危险及其预防及其预防和预防和治疗上。