Spaceflight exposome/microgravity effects on the psychoimmunoneuroendocrine system

Spaceflight missions represent a new exposome, unpredicted by evolution. Life-threatening agents activate non-specific stress responses involving the psycho-immune-neuroendocrine network. The main molecular pathways regulating this network and those affected by spaceflight exposome/microgravity are reported in various experimental setups. They include gut microbiota-derived metabolites, potentially valuable for countermeasure development. Meaningfully, the application of neuromodulation techniques, like the non-invasive transcutaneous vagal stimulation, for the prevention of pathophysiological alterations related to stress responses, is discussed.