Early Life Stress and Cardiovascular Disease Risk: Identifying the Role of Microbial Metabolites

早期生活压力和心血管疾病风险:确定微生物代谢物的作用

基本信息

  • 批准号:
    10739155
  • 负责人:
  • 金额:
    $ 17.05万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-08-01 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT: Exposure to early life stress (ELS), including abuse, neglect, and household dysfunction, significantly increases the risk of mental illness, chronic kidney disease, and cardiovascular disease (CVD) later in life. The previously characterized effects ELS and chronic disease development in adults may have their origins in ELS- dependent effects on composition and functions of the gut microbiota. The gut microbiota interact directly with the host’s immune and neurological systems and microbial derived metabolites have been shown to mediation cardiovascular function. My recently published research using a mouse model of ELS has determined that ELS alters the gut microbiota independent of maternal inheritance. This suggests ELS-medicated endogenous factors within the offspring are responsible for the ELS microbial phenotype. However, it remains unknown whether ELS-mediated changes in the gut microbiota play a direct role in the genesis risk factors for CVD. This proposal will address these knowledge gaps by identifying ELS-medicated factors that regulate the gut microbiota and elucidating microbial-mediated pathways that lead to increased CVD risk due to ELS. Adolescents and young adults with ELS have increased arterial stiffness and systemic vascular resistance. Using an established mouse model of ELS involving maternal separation, our novel data indicate that ELS is also associated with increased arterial stiffness in adolescent and adult mice. Furthermore, ELS induces superoxide production and endothelial dysfunction in adult mice. This suggests that vascular dysfunction is an important mediator of ELS-induced CVD risk. Our new data in mice show that ELS leads to reduced gut microbial diversity, lower circulating short-chain-fatty acids (SCFAs), and impaired gut barrier function during adolescence. Gut microbial diversity is negatively associated with arterial stiffness in women and reduced SCFAs are associated with hypertension and impaired gut barrier function. This suggests a role for the gut microbiota in ELS-induced vascular dysfunction, though exact mechanisms remain undefined. Therefore, the overall goal of this proposal is to elucidate mechanisms by which microbial metabolites mediate ELS-induced aortic stiffening and endothelial dysfunction and examine the potential of diet in the early intervention of CVD risk.
项目摘要/摘要: 暴露于早期生活压力(ELS),包括虐待、忽视和家庭功能障碍 增加精神疾病、慢性肾脏疾病和心血管疾病(CVD)的风险。这个 先前表征的ELS效应和成人慢性病的发展可能起源于ELS- 对肠道微生物区系组成和功能的依赖效应。肠道微生物区系直接与 宿主的免疫和神经系统以及微生物衍生的代谢物已被证明是 心血管功能。我最近发表的一项使用ELS小鼠模型的研究确定ELS 改变肠道微生物区系,独立于母体遗传。这表明ELS药物是内源性的 后代体内的因素是ELS微生物表型的原因。然而,它仍然是未知的 ELS介导的肠道微生物区系变化是否在CVD的发生风险因素中起直接作用。这 一项提案将通过确定调节肠道的ELS药物因子来解决这些知识差距 微生物区系和阐明导致ELS导致心血管疾病风险增加的微生物介导的途径。 患有ELS的青少年和年轻人动脉僵硬和全身血管增加 抵抗。使用建立的涉及母体分离的ELS小鼠模型,我们的新数据表明 ELS还与青春期和成年小鼠动脉僵硬增加有关。此外,ELS 诱导成年小鼠产生超氧化物和内皮功能障碍。这表明血管 功能障碍是ELS诱发心血管疾病风险的重要中介因素。我们在老鼠身上的新数据显示ELS导致 肠道微生物多样性降低,循环短链脂肪酸(SCFA)减少,肠道屏障受损 在青春期起作用。女性肠道微生物多样性与动脉僵硬呈负相关 而SCFAs减少与高血压和肠道屏障功能受损有关。这暗示着一种角色 对于ELS诱导的血管功能障碍中的肠道微生物区系,尽管确切的机制仍不清楚。 因此,这项提议的总体目标是阐明微生物代谢物 早期干预ELS诱导的主动脉硬化和内皮功能障碍并检测饮食的潜力 心血管疾病风险的干预。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Keri Kemp其他文献

Keri Kemp的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

相似海外基金

Identification of Prospective Predictors of Alcohol Initiation During Early Adolescence
青春期早期饮酒的前瞻性预测因素的鉴定
  • 批准号:
    10823917
  • 财政年份:
    2024
  • 资助金额:
    $ 17.05万
  • 项目类别:
Socio-Emotional Characteristics in Early Childhood and Offending Behaviour in Adolescence
幼儿期的社会情感特征和青春期的犯罪行为
  • 批准号:
    ES/Z502601/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.05万
  • 项目类别:
    Fellowship
Cognitive and non-cognitive abilities and career development during adolescence and adult development: from the perspective of genetic and environmental structure
青春期和成人发展期间的认知和非认知能力与职业发展:从遗传和环境结构的角度
  • 批准号:
    23K02900
  • 财政年份:
    2023
  • 资助金额:
    $ 17.05万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Reasoning about Spatial Relations and Distributions: Supporting STEM Learning in Early Adolescence
空间关系和分布的推理:支持青春期早期的 STEM 学习
  • 批准号:
    2300937
  • 财政年份:
    2023
  • 资助金额:
    $ 17.05万
  • 项目类别:
    Continuing Grant
Does social motivation in adolescence differentially predict the impact of childhood threat exposure on developing suicidal thoughts and behaviors
青春期的社会动机是否可以差异预测童年威胁暴露对自杀想法和行为的影响
  • 批准号:
    10785373
  • 财政年份:
    2023
  • 资助金额:
    $ 17.05万
  • 项目类别:
Mapping the Neurobiological Risks and Consequences of Alcohol Use in Adolescence and Across the Lifespan
绘制青春期和整个生命周期饮酒的神经生物学风险和后果
  • 批准号:
    10733406
  • 财政年份:
    2023
  • 资助金额:
    $ 17.05万
  • 项目类别:
The Role of Sleep in the Relationships Among Adverse Childhood Experiences, Mental Health Symptoms, and Persistent/Recurrent Pain during Adolescence
睡眠在不良童年经历、心理健康症状和青春期持续/复发性疼痛之间关系中的作用
  • 批准号:
    10676403
  • 财政年份:
    2023
  • 资助金额:
    $ 17.05万
  • 项目类别:
Thalamo-prefrontal circuit maturation during adolescence
丘脑-前额叶回路在青春期成熟
  • 批准号:
    10585031
  • 财政年份:
    2023
  • 资助金额:
    $ 17.05万
  • 项目类别:
Interdisciplinary Perspectives on the Politics of Adolescence and Democracy
青少年政治与民主的跨学科视角
  • 批准号:
    EP/X026825/1
  • 财政年份:
    2023
  • 资助金额:
    $ 17.05万
  • 项目类别:
    Research Grant
An Empirical Study on the Influence of Socioeconomic Status in Adolescence on Exercise Habits in Adulthood
青春期社会经济地位对成年期运动习惯影响的实证研究
  • 批准号:
    23K16734
  • 财政年份:
    2023
  • 资助金额:
    $ 17.05万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了