Researchers still struggle to understand the complex processes by which psychosocial factors like chronic stress increase disease susceptibility. This project will elucidate mechanistic pathways in the bidirectional stress-obesity relation, i.e. the mediating role of food choice, low-grade inflammation and disturbed gut microbiota. Observational and interventional research will be combined in community samples and clinical samples during childhood: (a) longitudinal pathways in existing cohorts with detailed background information; (b) contrasting groups on depression and overweight to unravel individual risk factors; and (c) two innovating interventions to substantiate new treatments by effects on inflammation, gut microbiota, stress sensitivity and energy-homeostasis i.e. probiotics in depression and emotional regulation training in obesity. We will have detailed gut microbiota sequencing and inflammation-status information; additional metabolomics data; both psychological and biological indicators of the stress status and laboratory induced stress reactivity; objectively measured adiposity parameters. A multidisciplinary and international collaboration with high scientific output is foreseen. Implications are multidisciplinary: (a) Raise public health attention to psychological well-being and a healthy diet; (b) Help basic science to enable mechanistic insights; (c) Inform clinical practice on pharmacological targets, psychological interventions and dietary guidelines.