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

项目摘要 一项快速增长的动物模型文献表明，微生物在大脑-肠轴 寄生在宿主肠道的肠道微生物区系会影响与两者相关的大脑功能 记忆功能和类似抑郁的行为。在人类中，糟糕的情节记忆与 抑郁症的发展和持续，但证据与肠道微生物群有关 有记忆的作文是有限的。关于人类微生物群关系的研究 与情绪障碍相关的成分、记忆表现和因素通常有 样本量小，结果适中。尽管这些研究中有许多使用了益生菌 为了改善记忆或症状，使用的益生菌类型要么来自 使用啮齿动物模型或一般向公众提供的模型进行研究。考虑到缺乏 啮齿动物和人类稳定的肠道微生物群组与非啮齿动物肠道微生物群组的一致性 对于商业上可获得的益生菌的特殊性，更有效的方法可能是 确定人类稳定的肠道微生物区系与记忆功能相关的变异。 解码人类肠道微生物区系的哪些特征与记忆有关将使 制定有针对性的微生物组干预措施。使用健康参与者的大样本 和有抑郁症状的患者，建议的研究将确定具体的 人类微生物区系变异性、情景记忆功能与早期生命的关系 压力，情绪障碍的一个公认的风险因素。解读人类的哪些特征 肠道微生物区系都与记忆力有关，会使发育更有效、更有针对性 微生物组干预。具体目标1下的分析将描述这种关系的特征 人类肠道微生物群组成的变异性与情景记忆的关系 性能。《特定目标2》的分析将探索早期生活压力在中介中的作用 微生物区系变异性与情景记忆的关系。确定特定的 微生物区系变异性、情景记忆功能和早期生活应激之间的关系是 发展有针对性的肠道微生物区系干预以增强发病的关键一步 记忆和降低情绪障碍的风险。

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.