EFFECTS OF INFANT NUTRITION ON FECAL RESISTOME ESTABLISHMENT
婴儿营养对粪便抵抗力建立的影响
基本信息
- 批准号:9180554
- 负责人:
- 金额:$ 14.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-07-01 至 2021-04-30
- 项目状态:已结题
- 来源:
- 关键词:AdolescentAffectAge-MonthsAgricultureAliquotAntibiotic ResistanceAntibiotic-resistant organismAntibioticsApplied SkillsArchivesAreaBacteriaBifidobacteriumBioinformaticsBiometryBreast FeedingCarbapenemsCattleCephalosporinsChildChild health careChildhoodClinicalCollectionCommunitiesCommunity DevelopmentsComplementComplexComputational BiologyCoupledDataData SetDatabasesDevelopmentDietDoctor of PhilosophyEnteralEpidemiologyExposure toFecesFoodFutureGastroenterologyGenerationsGeneticGenomeGenomicsGenotypeGoalsHealthHumanHuman MicrobiomeInfantInfectionInformed ConsentInstitutional Review BoardsInvestigationKnowledgeLaboratoriesLeadLearningLifeLinkLongitudinal StudiesMentorsMentorshipMetabolicMetagenomicsMicrobiologyMilkMonobactamsMothersNeonatalNeonatologyOrganismOutcomePhenotypePhylogenetic AnalysisPhysiciansPropertyPublicationsResearchResearch PersonnelResearch Project GrantsResistanceResolutionSamplingScienceScientistShotgun SequencingSiblingsSoilSolidSourceSoy MilkStructureSurveysSystems BiologyTaxonTechniquesTestingTimeTrainingTranslatingTranslational ResearchTwin Multiple BirthWhole-Genome Shotgun SequencingWorkbacterial resistancebasebeta-Lactam Resistancebeta-Lactamscareerclinically actionableclinically relevantcohortcombatcomputer frameworkcomputer programcritical periodexperiencefeedinggut microbiotainfancyinfant nutritioninnovationinterestmicrobialmicrobial communitymicrobiomemicrobiotanext generation sequencingnovelnovel strategiespathogenprogramsresistance geneskillssoystatisticstechnology developmenttooltrend
项目摘要
Project Summary
My research interests include the development of the neonatal enteric microbiome, with a current focus
on community-encoded functions such as antibiotic resistance or metabolic functions. I have worked since
2009 in the laboratory of Gautam Dantas, Ph.D.; during this time I have become proficient in a variety of
benchtop techniques necessary for work in microbiology and genomics research, have taken classes in
statistics and computer programming, and gained experience analyzing increasingly large and complex
collections of metagenomic data. I have collaborated with colleagues with expertise in genetics, microbiology,
gastroenterology, statistics, and neonatology, resulting in several publications. This proposal includes further
didactic training in bioinformatics and computational biology, with a focus on enhancing my skills and
knowledge in programming, statistics, and systems biology, as well as a research plan that will complement my
formal coursework by providing ample opportunity for me to apply these skills. I will continue to work with my
mentors Gautam Dantas, Ph.D., an expert in community-wide functions of human gut and soil bacteria and
Phillip Tarr, MD, an physician-scientist who is a leader in the field of pediatric microbiome research, and has a
track record of mentoring junior scientists to independence. My oversight committee includes Barak Cohen,
Ph.D., an expert in computational and systems biology, William Shannon, Ph.D., an expert in biostatistics, and
F. Sessions Cole, MD, an expert in genetics and translational research. The ongoing mentorship of these
collaborators with diverse areas of expertise will enhance my didactic and hands-on training and, combined
with my clinical experience as an academic neonatologist, will prepare me for an independent career as a
physician scientist investigating the impact of the human microbiome on neonatal health.
The research project described in this proposal is potentially clinically relevant, as bacterial resistance
to all antibiotics urgently threatens human health. The antibiotic resistance genes harbored by the human gut
microbiota (fecal resistome) are an epidemiologically important genetic reservoir that can potentially transfer
resistance to human pathogens. Understanding the clinical determinants of fecal resistance gene carriage may
lead to novel strategies to combat the spread of resistant organisms in human communities. Our recent work
has indicated that the fecal resistome of healthy children is far more diverse than previously suspected, and
suggests that the fecal resistome is established in early infancy, with infant resistomes being distinct from their
mothers' in by 1-2 months of life and developing similarly to their twin siblings'. The goal of this proposal is to
test the hypothesis that infant diet significantly influences fecal resistome and fecal microbial community
development.
Prior work by me and my mentors Dr. Dantas and Dr. Tarr has shown that functional metagenomic
selections are an efficient means of broadly sampling pediatric fecal resistomes. We will use high-throughput
functional metagenomic selections coupled with next-generation sequencing and a computational pipeline
developed in our lab (Parallel Assembly and Annotation of Functional Metagenomic Selections, PARFuMS) to
study longitudinal fecal resistome development in the first year of life in infants that are breastfed and formula
fed (cow's milk and soy formula both represented) with an emphasis on changes associated with feeding
transitions (e.g. from breastmilk to formula, initiating solid food). The samples to be used in this study have
already been collected with informed consent for a separate IRB-approved study, and are stored in the Dantas
lab. Functional metagenomic selections on a small subset of samples will be used to identify resistance genes
that are clinically important and unique to this cohort. We will use the phenotype-linked data generated by
functional metagenomic selections to quantify the correlation between specific resistance genes and genetic
motifs and resistance phenotypes, which will enhance existing resistance gene databases with functional
information and will provide a framework for identifying the most potentially dangerous resistance genes by
statistically linking them with undesirable resistance phenotypes. Shotgun sequencing of a much larger sample
set will allow high-resolution, quantitative data on the phylogenetic composition of the microbiota and predicted
microbiome-encoded functions. We will use this rich dataset to correlate clinical variables with changes in the
resistome, as well as to examine the effects of phylogenetic shifts on resistome development. This
comprehensive research strategy is novel because it will be, to our knowledge, the first longitudinal study of
the effects of early infant nutrition on fecal resistome and microbiome establishment, and will integrate
functional metagenomic techniques and whole-genome shotgun sequencing with novel computational
strategies developed expressly for longitudinal resistome study. The computational strategies developed for
this study will provide a theoretical framework for future longitudinal investigations of other community-wide
microbial functions. The work in this proposal will integrate with my clinical experience, my proposed didactic
training in bioinformatics, and my mentored experience with metagenomics to prepare me for a career as an
independent investigator conducting hypothesis-based research on thedevelopmental properties of the human
microbiome and translating this knowledge to impact child health outcomes.
项目总结
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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Aimee M Moore其他文献
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{{ truncateString('Aimee M Moore', 18)}}的其他基金
EFFECTS OF INFANT NUTRITION ON FECAL RESISTOME ESTABLISHMENT
婴儿营养对粪便抵抗力建立的影响
- 批准号:
9918341 - 财政年份:2016
- 资助金额:
$ 14.36万 - 项目类别:
EFFECTS OF INFANT NUTRITION ON FECAL RESISTOME ESTABLISHMENT
婴儿营养对粪便抵抗力建立的影响
- 批准号:
9307808 - 财政年份:2016
- 资助金额:
$ 14.36万 - 项目类别:
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