A road to remember: Neural plasticity through the lens of gut-brain interactions

The fact that the brain is influenced by the microorganisms that make up the gut microbiome substantially widens the scope of how we need to view human neurocognition and behaviour. However, a clear understanding of underlying mechanisms is scant and mainly grounded in animal work. This proposal aims at major contributions towards overcoming these limitations. The core hypothesis is that gut bacteria are key in shaping neural plasticity, and in this way, influence human memory abilities. Changes in gut microbial signalling may contribute to altered neurocognition in individuals who are genetically predisposed to Alzheimer’s disease. MemoryLane’s results will thus also have important implications for an ageing society. To systematically test the role of gut bacteria in neural plasticity, I will take a strong, theory-driven cognitive neuroscience approach. Under my lead, my research team will perform a fine-grained analysis of hippocampus-dependent memory and plasticity, using cognitive-behavioural testing and functional magnetic resonance imaging (fMRI) in healthy adults with and without a genetic risk for developing Alzheimer’s disease. Concomitant measures of gut microbial community structure will be essential. To establish causality, we will shape hippocampus-dependent plasticity and memory by modulating the gut microbiome with probiotic bacteria in a randomised, double-blind, placebo-controlled trial. This interdisciplinary approach will answer whether gut bacteria play a role in human neurocognition. Results will transform the way we understand memory processes, building translational bridges to prior animal and future clinical work. The insights gained may serve as a blueprint for pushing human gut-brain research to the next level, paving the way for potential interventions to alleviate the detrimental effects of altered gut-brain dynamics in genetic risk, older age, and disease.