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Population Genomic Analysis of Gut Microbial Colonization in Premature Infants

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:
10663304
负责人:
Jillian Banfield
金额:
$77.23万
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
未结题
起止时间:
2011-07-15 至 2026-06-30
关键词:
16S ribosomal RNA sequencingAdverse effectsAerobicAgreementAmpicillinAnaerobic BacteriaAncillary StudyAnimalsAntibiotic ResistanceAntibiotic TherapyAntibioticsAntimicrobial ResistanceBacteriaBacterial Antibiotic ResistanceBacterial ChromosomesBacterial GenesBacteriophagesBiologyBirthBlindedCell RespirationCessation of lifeChildhoodClinicalClinical TrialsCollectionDrug resistanceEarly DiagnosisEcosystemElementsEnrollmentEquipment and supply inventoriesExposure toFaceFormatesFundingGenesGenetic InductionGenomicsGentamicinsGestational AgeGrantHealthHospitalsHourHumanHuman MilkIncidenceInfantIntestinesIntravenousKnowledgeLengthLifeLinkLiteratureLongitudinal StudiesMeasuresMetabolismMetagenomicsMobile Genetic ElementsMothersMulticenter TrialsMutationNecrotizing EnterocolitisNeonatalNewborn InfantNitrogenOrganismOutcomeOutcome StudyOxidation-ReductionOxygenParticipantPatientsPatternPerinatalPlacebo ControlPlacebosPlasmidsPopulationPremature InfantProcessProtocols documentationRandomizedRectumReproductionResearchResistanceResolutionRibosomal RNASalineSamplingSampling StudiesSepsisStudy SubjectSwabTestingTimeTime Series AnalysisUnited States National Institutes of HealthVaginaVariantVertical Transmissionadverse outcomeantenatalclinically relevantearly onsetfitnessgut healthgut microbiomehuman datainfant gut microbiomeinter-individual variationknock-downlate onset sepsismaternal microbiomemembermicrobialmicrobial colonizationmicrobiomemicrobiome analysismicrobiome researchmicrobiotanovelopportunistic pathogenpathogenplacebo grouppreterm newbornprimary endpointrandomized placebo controlled trialrectalresistance generesistant strainsexstandard of caretranscriptomics

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英文摘要
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.
期刊论文(25)
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科研奖励(0)
会议论文
DOI: 10.1016/j.xcrm.2021.100393
发表时间: 2021-09-21
期刊: Cell reports. Medicine
影响因子: --
作者: [Lou YC, Olm MR, Diamond S, Crits-Christoph A, Firek BA, Baker R, Morowitz MJ, Banfield JF]
通讯作者: Banfield JF
DOI: 10.1016/j.isci.2021.102875
发表时间: 2021-08-20
期刊: iScience
影响因子: 5.8
作者: [Crisci MA, Chen LX, Devoto AE, Borges AL, Bordin N, Sachdeva R, Tett A, Sharrar AM, Segata N, Debenedetti F, Bailey M, Burt R, Wood RM, Rowden LJ, Corsini PM, van Winden S, Holmes MA, Lei S, Banfield JF, Santini JM]
通讯作者: Santini JM
DOI: 10.1038/s41467-023-43279-y
发表时间: 2023-11-16
期刊: Nature communications
影响因子: 16.6
作者: [Lou YC, Rubin BE, Schoelmerich MC, DiMarco KS, Borges AL, Rovinsky R, Song L, Doudna JA, Banfield JF]
通讯作者: Banfield JF
DOI: 10.1186/s40168-018-0493-5
发表时间: 2018-06-20
期刊: Microbiome
影响因子: 15.5
作者: [Brooks B, Olm MR, Firek BA, Baker R, Geller-McGrath D, Reimer SR, Soenjoyo KR, Yip JS, Dahan D, Thomas BC, Morowitz MJ, Banfield JF]
通讯作者: Banfield JF
11
    Expanding CRISPR-Cas editing technology through exploration of novel Cas proteins and DNA repair systems
    • 批准号:
      10215491
    • 项目类别:
    • 资助金额:
      $39.25万
    • 财政年份:
      2018
    • 负责人:
      Jillian Banfield
    • 依托单位:
    Expanding CRISPR-Cas editing technology through exploration of novel Cas proteins and DNA repair systems
    • 批准号:
      10459340
    • 项目类别:
    • 资助金额:
      $39.25万
    • 财政年份:
      2018
    • 负责人:
      Jillian Banfield
    • 依托单位:
    Expanding CRISPR-Cas editing technology through exploration of novel Cas proteins and DNA repair systems
    • 批准号:
      9768324
    • 项目类别:
    • 资助金额:
      $39.25万
    • 财政年份:
      2018
    • 负责人:
      Jillian Banfield
    • 依托单位:
    Proteogenomic analysis of inflammation and dysbiosis in the infant gut
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