The Neonatal Microbiome and Necrotizing Enterocolitis

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影响了一个容易识别的高危人群，具有严格的 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。

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.