The aim of this project is to explore the relationships between the gut microbiome (alpha- and beta diversity indices, gut microbial species/taxa, and functional pathways) and the risk of major chronic diseases as well as all-cause and cause-specific mortality. The specific aims are to: 1. Investigate the associations of the gut microbiome with risk of cardiovascular diseases—in this project, the focus is on MACE (composite outcome of ischemic heart disease, stroke, and CVD mortality), stroke, atrial fibrillation, heart failure, peripheral artery disease, and venous thromboembolism. 2. Evaluate the associations of the gut microbiome with prevalent and incident diabetes and components of the metabolic syndrome, such as fasting glucose, fasting insulin, blood lipids, and blood pressure. 3. Explore the association of the gut microbiome with risk of overall cancer and cancer at specific sites. 4. Assess the association between the gut microbiome and risk of dementia (any, AD, and vascular) and cognitive decline. 5. Examine the association between the gut microbiome and mortality, including all-cause and cause-specific mortality, as well as longevity.