Interestingly, NOD1 and NOD2 defense effects are only related with immunity because an elegant study has demonstrated that the lack of both receptors in mice leads to signs of stress-induced anxiety, cognitive impairment, and depression, together with increased GI permeability and altered serotonin signaling in the gut, suggesting that NOD1 and NOD2 are novel therapeutic targets for gut–brain axis disorders (156). This evidence concerns the gene NOD2 and Cognitive impairment.