Both psychiatric disorders and cognitive impairment are a leading cause of the global burden of health. Depression, anxiety, and stress-related disorders are common psychiatric disorders, with a higher prevalence in women than in men. The microbiota-gut-brain axis has been proposed as a candidate mechanism underlying mental disorders and cognitive impairment. Nevertheless, the evidence on the associations of gut microbiome with the risk of depression, anxiety, stress-related disorders, and cognitive impairment is weak. This is partly due to methodological limitations, such as small sample size and cross-sectional design, leading to distinct discrepancy in findings of previous studies. Regardless, although multiple genetic risk factors have been identified for psychiatric disorders and cognitive impairment, no study has to date assessed the interplay of genetic susceptibility to psychiatric disorders and cognitive impairment with gut microbiome on the risk of depression, anxiety, stress-related disorders, and cognitive impairment. Furthermore, gut microbiome may modulate the links of infection with psychiatric disorders and cognitive impairment. No previous studies, however, have assessed such effect modification of gut microbiome. Finally, antidepressants are the first-line treatment for patients with depression and have been reported to alter gut microbiota composition and functionality. Whether gut microbiome is associated with the treatment response to antidepressants is, however, largely unknown. The overarching aim of the project is therefore to understand the role of gut microbiota composition and functionality on the risk of depression, anxiety, stress-related disorders, and cognitive impairment as well as on the treatment response to antidepressants. Specifically, we aim to study: 1. the associations of gut microbiota composition and functionality with risk of depression, anxiety, stress-related disorders, and cognitive impairment; 2. the effect modification of genetic predisposition to psychiatric disorders (i.e., risk genes or polygenic risk score) in the associations between gut microbiome and depression, anxiety, stress-related disorders, and cognitive impairment; 3. the role of gut microbiota composition and functionality on modulating the link between infections (including COVID-19) and depression, anxiety, stress-related disorders, and cognitive impairment; 4. the associations of gut microbiota composition or functionality with the treatment response to antidepressants.