PROJECT: JTC2024 - Brain-Body: AnxBrGut

Susceptibility/resilience to psychiatric disorders depends on neural and non-neural factors that interact with adverse events at specific times in life to imprint lasting effects. We have developed a mouse model of peripubertal stress that induces susceptibility to anxiety, identified a brain circuit involved in this imprinting and found that the gut microbiota is affected, the latter being in constant dialogue with the brain. Our stress model offers a unique opportunity to study the brain and gut mechanisms that determine susceptibility/resilience to anxiety. With the complementary skills of an electrophysiology specialist, an expert in transcriptomics, epigenetics, a specialist in multi-omics studies of microbiota, and an expert in the gut-brain axis, we will identify the molecular and cellular changes induced by peripubertal stress and the alterations in the brain and microbiota responsible for susceptibility to anxiety in mice. We will identify metabolic signatures predictive of susceptibility/resistance and examine whether they are relevant in humans. We will identify critical communication pathways between brain and microbiota that lead to disease or resilience. Anxiety symptoms may affect up to 50% of individuals exposed to major stresses. Elucidation of the cellular, molecular, metabolic and microbial changes that predict anxiety susceptibility/resilience will provide new avenues to prevent or reverse the deleterious effect of stress in anxiety-prone individuals.