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.

坏死性小肠结肠炎（NEC）是一种影响约10%早产儿的毁灭性疾病。其死亡率仍然很高（15-30%），其原因尚不清楚。在住院的低出生体重新生儿中，约80%的病例发生在出生后35天内。益生菌可降低NEC的发生率和严重程度，且NEC不会在产前发生。NEC影响一个容易识别的高危人群，在发病前有一个严格定义的间隔，发生在与流动中的微生物种群密切相关的器官系统中，与肠道微生物群有似是而非的关联，并且很少对高危人群进行大量或前瞻性研究。因此，这种疾病提供了一个独特的机会来探索人类肠道微生物群在一种毁灭性疾病中的作用。此外，NEC流行病学和年龄发病率提供了招募和研究极有可能提供有价值的病理生理学和微生物学见解的队列的能力。