Neurobiological and neurocognitive consequences of diverse microbiome functional trajectories
不同微生物组功能轨迹的神经生物学和神经认知后果
基本信息
- 批准号:10443912
- 负责人:
- 金额:$ 72.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-01 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:4 year oldAgeAnabolismAnxietyAreaBacteriaBehaviorBiochemicalBiologicalBirthBlood specimenBrainChemicalsChildClinicalClinical ResearchCognitionCollectionCommunicationDataDevelopmentEnteric Nervous SystemEventExposure toFirst Pregnancy TrimesterFutureGoalsHuman MilkImmuneIndividual DifferencesInfantInterventionIntestinesLifeLinkMaternal ExposureMeasuresMetagenomicsModelingMolecularMothersNeurobiologyNeurocognitiveNeurotransmittersNewborn InfantOutcomeParticipantPathway interactionsPeripheralPhasePlacentaPlayPregnancyPrevention strategyProductionReportingRisk FactorsRoleSamplingShapesSignal TransductionSourceTaxonomyTestingThird Pregnancy TrimesterUmbilical Cord Bloodbasecohortdesignearly onsetendophenotypefeedinggut bacteriagut colonizationgut microbiomegut microbiotagut-brain axisimprintimprovedindexinginfant gut microbiomematernal anxietymaternal imprintmaternal microbiomematernal microbiotamaternal riskmetabolomicsmetagenomemicrobiomemicrobiome compositionmicrobiotamother nutritionneglectneurodevelopmentneuroimagingnutritionoffspringparent grantpostnatalpostnatal developmentpostnatal periodpre-clinicalprenatalprenatal exposureprenatal influenceprospectivevaginal fluidvaginal microbiome
项目摘要
There is compelling evidence for a critical role of the maternal and infant gut microbiome in early infant brain
neurodevelopment. Temporal milestones in postnatal infant gut microbiome development align with changes in
early infant brain development, suggesting functional relationships between these two pivotal events. The
premise of our proposal is based on a wealth of studies and new preliminary analyses reported below linking
maternal prenatal anxiety (PNA), a prominent prenatal maternal risk factor, and child neurodevelopment. We
hypothesize that the prenatal maternal microbiome and its influence on newborn neurodevelopment is shaped
by PNA, and that early infant cognition is determined by mother-to-infant microbiome transfer, postnatal
development and biosynthesis of microbiota-derived neuroactive metabolites (NAMs). Our study is framed by a
proposed developmental model that includes two major components; prenatal anxiety and developmental phase
trajectories of the infant gut microbiome. The proposed model has scientific as well as practical strengths, as it
leverages a wealth of existing data collected as part of a large, prospective longitudinal and diverse pregnancy
cohort that has been followed from the first trimester through the child’s 4th year, with extensive longitudinal
characterization of prenatal exposures, child microbiome and other key biological samples, and child
neurodevelopment assessed longitudinally that will enable important and previously neglected incorporation of
potential confounds. We use these components to test the central hypothesis that neurodevelopment is
dependent on age-driven biosynthesis of NAMs through the postnatal period of infant gut-microbiome (IGM)
development. In Aim 1, we use metagenomic analysis of the prenatal maternal vaginal microbiome (MVM) to
identify species and functional biosynthetic pathways for NAMs associated with PNA. We also assess the
potential transfer of maternal anxiety through the initial colonization of the infant gut microbiome by an anxiety
“imprinted” MVM. In Aim 2, we use metagenomic and metabolomic analyses to determine the association
between key stages of IGM development and differential synthesis of NAMs over the first year, attending to
confounds and competing exposures, most notably, maternal diet and infant feeding. In Aim 3, we apply this rich
data to predict neurocognitive assessments from age 1 to 4 years to formally test the temporal relationship
between microbiome phase and neurodevelopment in the first year of life and durability of the microbiota-
neurodevelopment relationship through 4 years of age. The scientific impact of the study will be on advanced
understanding of the role of prenatal exposures; documenting sources of between- and within-individual
differences in the IGM through the first years of life; identifying NAMs with a possible mechanistic role in the
MGB axis; documenting a potentially broad and persistent impact on neurodevelopment.
有令人信服的证据表明,母婴肠道微生物组在婴儿早期大脑中起着关键作用
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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STEVEN R. GILL其他文献
STEVEN R. GILL的其他文献
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{{ truncateString('STEVEN R. GILL', 18)}}的其他基金
Understand biological factors underlying early childhood caries disparity from the oral microbiome in early infancy
从婴儿早期口腔微生物组了解儿童早期龋齿差异背后的生物因素
- 批准号:
10765136 - 财政年份:2022
- 资助金额:
$ 72.32万 - 项目类别:
Understand biological factors underlying early childhood caries disparity from the oral microbiome in early infancy
从婴儿早期口腔微生物组了解儿童早期龋齿差异背后的生物因素
- 批准号:
10666930 - 财政年份:2022
- 资助金额:
$ 72.32万 - 项目类别:
Understand biological factors underlying early childhood caries disparity from the oral microbiome in early infancy
从婴儿早期口腔微生物组了解儿童早期龋齿差异背后的生物学因素
- 批准号:
10443354 - 财政年份:2022
- 资助金额:
$ 72.32万 - 项目类别:
Neurobiological and neurocognitive consequences of diverse microbiome functional trajectories
不同微生物组功能轨迹的神经生物学和神经认知后果
- 批准号:
10651895 - 财政年份:2022
- 资助金额:
$ 72.32万 - 项目类别:
Understand biological factors underlying early childhood caries disparity from the oral microbiome in early infancy
从婴儿早期口腔微生物组了解儿童早期龋齿差异背后的生物学因素
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10612957 - 财政年份:2022
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