Abstract
Cardiometabolic disease (CMD) is a leading cause of death worldwide and encompasses the inflammatory metabolic disorders of obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and cardiovascular disease. Flavonoids are polyphenolic plant metabolites that are abundantly present in fruits and vegetables and have biologically relevant protective effects in a number of cardiometabolic disorders. Several epidemiological studies underscored a negative association between dietary flavonoid consumption and the propensity to develop CMD. Recent studies elucidated the contribution of the gut microbiota in metabolizing dietary intake as it relates to CMD. Importantly, the biological efficacy of flavonoids in humans and animal models alike is linked to the gut microbial community. Herein, we discuss the opportunities and challenges of leveraging flavonoid intake as a potential strategy to prevent and treat CMD in a gut microbe-dependent manner, with special emphasis on flavonoid-derived microbial metabolites.