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

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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.