We and other researchers have shown that modifiable factors, including diet, certain beverages (e.g., coffee, sweetened beverages, and milk), excess adiposity, physical activity, and smoking play an important role in the development of cardiometabolic outcomes, like type 2 diabetes, hypertension, hypercholesterolemia, and cardiovascular diseases (CVD). With regard to diet, the Dietary Approaches to Stop Hypertension diet has been found to reduce blood pressure and the risk of cardiovascular diseases. Likewise, it has been shown that a plant-based diet rich in healthier plant foods is associated with lower risks CVD. Emerging evidence also indicates that modifiable factors are associated with gut microbiota composition, and that gut microbiota and associated metabolites are implicated in the development of cardiometabolic outcomes. Nevertheless, few associations have been replicated and few studies have examined whether the modifiable factors-outcome associations may be mediated, at least in part, by gut microbiota and related metabolites.