PROJECT: JTC2024 - Brain-Body: MOODYGUT

The overarching goal of this transnational project is to uncover the mechanisms through which specific microbial strains contribute to depression traits in a sex-specific manner. To achieve this, we will analyse human microbiome data from individuals with depression and related mood disorders, with or without inflammatory bowel disease (IBD), alongside a well-established rodent model of depression. Through extensive cooperation among consortium partners from Germany, Switzerland, and Israel, we will: 1) Characterize gut microbial strains in humans significantly associated with anxiety and depression symptoms. 2) Investigate changes in microbiota and immune responses in stress-susceptible and resilient mice subjected to repeated social defeat stress (RSDS), a murine depression model, and relate these changes to hippocampal functions implicated in disease progression. 3) Explore whether specific microbiomes or their associated metabolites can alleviate depression symptoms and modify underlying intestinal, immunological, and neurological pathways by introducing isolated strains into germ-free and antibiotic-treated mice, with or without RSDS experience. 4) Examine the causal role of the vagus nerve, a key mediator of the gut-brain axis, in depression traits. We anticipate that the insights gained from this study will pave the way for treatments aimed at restoring the body's innate mechanisms for repairing protective functions lost during depression.