Early Life Stress Patterning of the Gut-Brain Axis: An Intergenerational Approach
肠-脑轴的早期生命压力模式:代际方法
基本信息
- 批准号:10057964
- 负责人:
- 金额:$ 10.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-01 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcetatesAcidsAddressAdultAffectAfrican AmericanAge-MonthsBacteriaBlood specimenBrainButyratesC-reactive proteinCaproatesCaucasiansChild AbuseChildhoodChronic stressComplexConsumptionDataDevelopmentDietDietary intakeEnterobacteriaceaeEubacteriumFamilyFecesFetal healthFutureGrowthHealthHigh Risk WomanImmune systemInfantInflammationInflammatoryIntakeInterleukin-1Interleukin-6InterventionIntestinesLaboratoriesLeadLifeLinkLow Birth Weight InfantMeasuresMediatingMediator of activation proteinModelingMothersNeuroimmuneNeurosecretory SystemsNutrientOmega-3 Fatty AcidsOutcomePatternPediatric HospitalsPeripheralPhiladelphiaPhysiologicalPilot ProjectsPopulationPregnancyPregnant WomenPremature BirthPrevotellaProductionPropionatesPsychiatric DiagnosisPublishingRecording of previous eventsResearchRiskRodent ModelRoleSamplingSerumShapesShotgunsStressTNF geneThird Pregnancy TrimesterVaginal delivery procedureValeratesVertical Disease TransmissionVolatile Fatty AcidsWomanWorkadverse childhood eventsbacterial communitybasebeta diversitybiological adaptation to stresscohortcytokineearly experienceearly life stressgut microbiomegut microbiotagut-brain axishigh riskindexinginfant outcomeinflammatory disease of the intestineintergenerationallymphotoxin betametabolomemetabolomicsmetagenomic sequencingmicrobial communitymicrobiomemicrobiome alterationmother nutritionneglectneurodevelopmentnoveloffspringpre-clinical researchpregnantprogramsstool samplestressor
项目摘要
PROJECT SUMMARY
Adverse childhood experiences (ACEs), such as abuse or chronic stress, program a dysregulated
neuroendocrine-neuroimmune axis that persists through adulthood and promotes elevated inflammation. A
proinflammatory milieu during pregnancy may be particularly pernicious, with potential health effects on both
mother and offspring. In African American (AA) women, childhood stress is associated with poor infant
outcomes, independent of adulthood stress exposure. AA women have higher rates of ACE exposure and
greater physiologic vulnerability to the inflammatory impact of stress than Caucasian women, and double the
rate of preterm birth as Caucasians in the U.S., underlining the importance of studying stress and maternal-
offspring health in this population. Data from our laboratory suggests that the gut microbiome may be a key link
in the association between maternal ACE and elevated inflammation in pregnancy. While there are links
between gut microbial composition and elevated proinflammatory cytokines, a gap in the research remains in
establishing links from ACE to gut microbiome to inflammation, which our first aim addresses. Further, if ACE
is associated with an altered gut microbiome during pregnancy, does this altered microbiome pass to the
offspring during vaginal delivery? Our second aim addresses whether stress-induced alterations in the
maternal gut microbiome are passed to the offspring, assessing offspring gut microbial community composition
and metabolites (the metabolome). As the gut microbiome-metabolome shapes development of the offspring
immune system and makes nutrients available for brain development, its function has important implications for
offspring outcomes. Finally, our laboratory found that maternal dietary intake of omega-3 fatty acids may
ameliorate the effects of ACE on inflammation during pregnancy. In women with a history of multiple ACEs
(“high ACE”), those who consumed large amounts of omega-3 fatty acids had an inflammatory stress response
similar to that of women with no ACE history, while high ACE women with low omega-3 consumption had
elevated levels of proinflammatory cytokines. Our final aim assesses impact of maternal diet during pregnancy
on the relationship between gut microbiome and inflammation, with implications for future intervention work in
this high-risk pregnant AA population. To address these aims, we will study 200 mother-infant dyads from the
existing Children’s Hospital of Philadelphia (CHOP) Infant Growth and Microbiome (IGRAM) cohort, with
existing fecal and blood samples. We will measure gut microbial community composition at the sub/species
level using leading-edge shotgun metagenomics sequencing, gut metabolites (short chain fatty acids; SCFAs)
as an index of gut function, and serum proinflammatory cytokines in mothers and offspring. This would allow us
to model the complex relationships among maternal ACEs, gut microbiome, and inflammation, and the
relationship of these factors between mother and offspring.
项目总结
不良童年经历(ACE),如虐待或慢性压力,计划失调
神经内分泌-神经免疫轴,在成年期持续存在,并促进炎症升高。一个
孕期的促炎环境可能特别有害,对双方都有潜在的健康影响。
母亲和后代。在非裔美国人(AA)女性中,童年压力与贫穷的婴儿有关
结果,独立于成年期的压力暴露。AA女性有更高的ACE暴露和
比高加索女性更容易受到压力的炎症影响,并且是高加索女性的两倍
美国高加索人的早产率,强调了研究压力和母亲的重要性--
在这个群体中的后代健康。我们实验室的数据表明,肠道微生物群可能是一个关键环节
孕妇血管紧张素转换酶与妊娠炎症升高之间的关系。虽然有链接
在肠道微生物组成和升高的促炎细胞因子之间,研究中的差距仍然存在
建立从ACE到肠道微生物组再到炎症的联系,这是我们的首要目标。此外,如果ACE
与怀孕期间肠道微生物群的改变有关,这种改变的微生物群是否会传递给
在阴道分娩过程中的后代?我们的第二个目标是解决应激诱导的
母体肠道微生物群传递给子代,评估子代肠道微生物群落组成
和代谢物(代谢体)。随着肠道微生物代谢组形成后代的发育
免疫系统,并为大脑发育提供营养物质,其功能对
后代的结果。最后,我们的实验室发现,母亲饮食中摄入omega-3脂肪酸可能会
血管紧张素转换酶对妊娠期炎症的影响有多个A级病史的女性
(“高ACE”),那些大量摄入omega-3脂肪酸的人有炎症应激反应
与没有ACE病史的女性相似,而ACE水平高、omega-3摄入量低的女性有
促炎症细胞因子水平升高。我们的最终目标是评估孕期母亲饮食的影响
肠道微生物群与炎症的关系及其对未来干预工作的启示
这些高危的再生障碍性贫血孕妇。为了达到这些目标,我们将研究200个母婴双胞胎
现有的费城儿童医院(CHOP)婴儿生长和微生物群(IGAM)队列,
现有的粪便和血液样本。我们将测量亚种/物种的肠道微生物群落组成
水平使用领先的鸟枪式元基因组测序,肠道代谢物(短链脂肪酸;SCFAs)
作为肠道功能和母子血清促炎细胞因子的指标。这将使我们能够
建立母体ACEs、肠道微生物群、炎症和
这些因素对母子关系的影响。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Liisa Victoria Hantsoo其他文献
Liisa Victoria Hantsoo的其他文献
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{{ truncateString('Liisa Victoria Hantsoo', 18)}}的其他基金
Allopregnanolone and Gamma-Aminobutyric Acid Receptor (GABA-A-R) Plasticity in Women with Premenstrual Mood Symptoms
四氢孕酮和 γ-氨基丁酸受体 (GABA-A-R) 可塑性对有经前情绪症状的女性
- 批准号:
10363837 - 财政年份:2022
- 资助金额:
$ 10.33万 - 项目类别:
Allopregnanolone and Gamma-Aminobutyric Acid Receptor (GABA-A-R) Plasticity in Women with Premenstrual Mood Symptoms
四氢孕酮和 γ-氨基丁酸受体 (GABA-A-R) 可塑性对有经前情绪症状的女性
- 批准号:
10619504 - 财政年份:2022
- 资助金额:
$ 10.33万 - 项目类别:
Early Life Stress Patterning of the Gut-Brain Axis: An Intergenerational Approach
肠-脑轴的早期生命压力模式:代际方法
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