Population Genomic Analysis of Gut Microbial Colonization in Premature Infants

早产儿肠道微生物定植的群体基因组分析

• 批准号: 10298678
• 负责人: Jillian Banfield
• 金额: $ 78.67万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10298678
• 关键词: 16S ribosomal RNA sequencing; Adverse effects; Aerobic; Agreement; Ampicillin; Anaerobic Bacteria; Ancillary Study; Animals; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Bacterial Antibiotic Resistance; Bacterial Chromosomes; Bacterial Genes; Bacteriophages; Biology; Birth; Blinded; Cell Respiration; Cessation of life; Childhood; Clinical; Clinical Trials; Collection; Drug resistance; Early Diagnosis; Ecosystem; Elements; Enrollment; Equipment and supply inventories; Exposure to; Face; Funding; Genes; Genetic; Genomics; Gentamicins; Gestational Age; Grant; Health; Hospitals; Hour; Human; Human Milk; Incidence; Infant; Intestines; Intravenous; Knowledge; Length; Life; Link; Literature; Longitudinal Studies; Measures; Metabolism; Metagenomics; Mothers; Multicenter Trials; Mutation; Necrotizing Enterocolitis; Neonatal; Newborn Infant; Nitrogen; Organism; Outcome; Outcome Study; Oxidation-Reduction; Oxygen; Participant; Patients; Pattern; Perinatal; Placebo Control; Placebos; Plasmids; Population; Premature Infant; Process; Protocols documentation; Randomized; Research; Resistance; Resolution; Ribosomal RNA; Saline; Sampling; Sampling Studies; Sepsis; Study Subject; Swab; Testing; Time; Time Series Analysis; United States National Institutes of Health; Vagina; Variant; Vertical Disease Transmission; adverse outcome; antenatal; clinically relevant; early onset; fitness; gut health; gut microbiome; infant gut microbiome; inter-individual variation; knock-down; late onset sepsis; maternal microbiome; member; microbial; microbial colonization; microbiome; microbiome analysis; microbiome research; nano; novel; opportunistic pathogen; pathogen; placebo group; preterm newborn; primary endpoint; randomized placebo controlled trial; rectal microbiome; resistance gene; resistant strain; sex; standard of care; transcriptomics

Abstract A large body of literature now indicates that antenatal and neonatal antibiotic exposure is associated with adverse childhood outcomes due to disruption of the developing microbiome. In premature infants, the standard of care for many decades has included the administration of broad-spectrum antibiotics in the first hours of life as treatment for a presumptive diagnosis of early onset sepsis. However, nearly all preterm infants receiving these antibiotics do not actually have sepsis. This grant renewal application proposes an ancillary microbiome study linked to the NANO (NICU Antibiotics and Outcomes) Trial, a recently launched clinical trial that will challenge this longstanding practice of immediately prescribing antibiotics to newborn preterm infants. NANO will test the hypothesis that antibiotics at birth worsens outcomes in preterm infants that are clinically stable. This multicenter trial, which is led by members of our research team, will randomize 802 premature infants to receive intravenous ampicillin and gentamicin or a saline placebo control. The study will measure the impact of variables including mode of delivery, gestational age, sex, and receipt of maternal milk, and administration of maternal antepartum antibiotics. Infant fecal samples in the first month of life as well as maternal fecal and vaginal swabs will be collected in NANO for basic microbiome profiling in the antibiotics and placebo groups using 16S rRNA gene sequencing. Here, we propose to augment microbiome analyses of NANO study subjects using novel strain-level metagenomic strategies and by analyzing samples beyond the first month of life. With this strategy, we propose to Aim 1. Test the hypothesis that empiric antibiotics (EA) disrupts mother-infant strain sharing in preterm infants. Aim 2. Test the hypothesis that EA increases the abundance of gut bacterial antimicrobial resistance genes in preterm infants. Aim 3. Test the hypothesis that EA delays the transition from a gut ecosystem dominated by facultative anaerobes to one dominated by obligate anaerobes. Because NANO is a first-of-its-kind clinical trial evaluating antibiotic therapy during the first days of life, this ancillary study will provide a rare opportunity to ask and answer a unique set of questions about the biology of early gut bacterial colonization.

抽象的 现在，大量文献表明产前和新生儿抗生素暴露与不利有关 由于发育中的微生物组的破坏而导致的童年结果。在早产婴儿中，护理标准 数十年来，包括在生命的头几个小时内管理广谱抗生素的管理 对早期败血症进行推定诊断的治疗。但是，几乎所有的早产儿都接受了这些 抗生素实际上没有败血症。该赠款更新申请提出了辅助微生物组研究 与Nano（NICU抗生素和结果）试验有关，该试验将挑战最近发起的临床试验 这种长期以来立即开药抗生素对新生早产儿处开的习惯。纳米将测试 假设出生时抗生素会使临床稳定的早产儿的结局恶化。这个多中心 由我们的研究团队成员领导的试验将使802名早产儿随机接受静脉注射 氨苄青霉素和庆大霉素或盐分安慰剂控制。该研究将衡量变量的影响，包括 分娩方式，胎龄，性别和母乳接收以及母亲的给药 抗生素。 婴儿粪便样品在生命的第一个月以及母体粪便和阴道拭子将收集 使用16S rRNA基因测序的抗生素和安慰剂组中基本微生物组分析的纳米。 在这里，我们建议使用新型应变水平来增强纳米研究对象的微生物组分析 宏基因组策略以及分析生命的第一个月以外的样本。通过这种策略，我们提出了 目标1。检验以下假设：经验性抗生素（EA）破坏了早产儿的母菌株共享。 AIM 2。检验以下假设：EA增加了肠道细菌抗菌抗性基因的丰度 早产婴儿。目标3。检验EA从肠道生态系统延迟的假设 兼性厌氧菌的厌氧菌是由专性厌氧占主导地位的。因为Nano是首个临床试验 在生命的第一天评估抗生素疗法，这项辅助研究将为难得的机会询问 并回答有关早期肠道细菌定植的生物学的独特问题。