Gut Microbiome Contributions to Human Episodic Memory and the Role of Early Life Stress

肠道微生物组对人类情景记忆的贡献以及早期生活压力的作用

• 批准号: 10726345
• 负责人: Elizabeth Anya Phelps
• 金额: $ 46.48万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10726345
• 关键词: Adult; Animal Model; Antibiotics; Bacteria; Behavior; Bifidobacterium; Brain; Cognitive; Data; Depressive disorder; Development; Disease; Distress; Emotional; Emotional disorder; Environment; Episodic memory; Future; Germ-Free; Goals; Human; Human Microbiome; Impairment; Individual; Intervention; Intervention Studies; Intestines; Lactobacillus plantarum; Link; Literature; Mediating; Memory; Memory Disorders; Memory impairment; Mental Depression; Meta-Analysis; Mood Disorders; Mus; Nature; Participant; Patients; Performance; Population; Probiotics; Reporting; Research; Risk Factors; Risk Reduction; Rodent; Rodent Model; Role; Sample Size; Sampling; Short-Term Memory; Symptoms; System; Techniques; Variant; Verbal Learning; Woman; depressive symptoms; early experience; early life stress; emotional behavior; gut microbes; gut microbiome; gut microbiota; gut-brain axis; high risk; human microbiota; improved; insight; memory recognition; microbiome; microbiome composition; microbiota; microbiota profiles; microorganism; novel; pathogenic bacteria; prevent; stress reactivity

Project Summary A rapidly growing literature in animal models suggests a brain-gut axis where microorganisms inhabiting the host intestinal tract, the gut microbiota, impact brain functions related to both memory function and depressive-like behaviors. In humans, poor episodic memory is linked to the development and perpetuation of depression, but evidence linking gut microbiome composition with memory is limited. Studies examining the relation between human microbiome composition, memory performance and factors related to emotional disorders generally have small sample sizes and modest results. Although many of these studies use probiotic manipulations to improve memory or symptoms, the type of probiotic used is either derived from research with rodent models or one that is generally available to the public. Given the lack of concordance between stable gut microbiome profiles in rodents and humans, and the non- specific nature of commercially available probiotics, a more effective approach might be to identify variations in stable gut microbiota profiles in humans associated to memory function. Decoding which features of the human gut microbiota are related to memory would enable the development of targeted microbiome interventions. Using a large sample of healthy participants and patients with depressive symptoms, the proposed research will identify the specific relationship between human microbiota variability, episodic memory function and early life stress, an established risk factor for emotional disorders. Decoding which features of the human gut microbiota are related to memory would enable the development of more effective, targeted microbiome interventions. Analyses under Specific Aim 1 will characterize the relationship between variability in gut microbiome composition in humans and episodic memory performance. Analyses under Specific Aim 2 will explore the role of early life stress in mediating the relationship between microbiota variability and episodic memory. Identifying the specific relationship between microbiota variability, episodic memory function and early life stress is a critical step in the development of targeted gut microbiota interventions to enhance episodic memory and reduce the risk of emotional disorders.

项目摘要 在动物模型中迅速增长的文献表明，微生物存在脑-肠轴， 居住在宿主肠道，肠道微生物群，影响与两者相关的大脑功能 记忆功能和抑郁样行为。在人类中，情节记忆差与 抑郁症的发展和延续，但证据表明肠道微生物组 具有记忆的组合物是有限的。研究人类微生物组之间的关系 成分、记忆表现和与情绪障碍有关的因素通常具有 小样本和适度的结果。虽然这些研究中有许多使用益生菌 为了改善记忆或症状，所使用的益生菌类型要么来自 啮齿类动物模型的研究或一般向公众提供的研究。由于缺乏 啮齿动物和人类稳定肠道微生物组谱之间的一致性，以及非 由于市售益生菌的特殊性质，更有效的方法可能是 确定与记忆功能相关的人类稳定肠道微生物群特征的变化。 解码人类肠道微生物群的哪些特征与记忆有关， 制定有针对性的微生物组干预措施。使用大量健康参与者样本 和有抑郁症状的患者，拟议的研究将确定具体的 人类微生物群变异性、情景记忆功能和早期生命之间的关系 压力，一个确定的情绪障碍的危险因素。解码人类的哪些特征 肠道微生物群与记忆有关，将使发展更有效，有针对性的 微生物干预。具体目标1下的分析将描述这种关系 人类肠道微生物组组成的变异性与情景记忆之间的关系 性能具体目标2下的分析将探讨早期生活压力在介导 微生物群变异性和情景记忆之间的关系。识别特定 微生物群变异性，情景记忆功能和早期生活压力之间的关系是一个 发展有针对性的肠道微生物群干预措施以增强间歇性 记忆力和减少情绪障碍的风险。