The molecular mechanisms by which dietary fruits and vegetables confer health benefits remain poorly understood. Historically, beneficial properties in the amelioration of conditions like cardiometabolic disease or intestinal cancer have been attributed to the antioxidant activity of flavonoids. However, flavonoids are consumed in a largely glycosylated form, rendering them poorly available for small intestinal absorption and subsequent systemic distribution. Upon reaching the colon, select commensal gut bacteria can catabolize these flavonoid substrates into smaller monophenolic acids. Our lab uses several mouse disease models to assess the contribution of microbial catabolism to the beneficial effects exerted by dietary flavonoids. In a diet-induced obesity model, we identified gut microbial flavonoid catabolites, which on their own are sufficient to reduce cardiometabolic disease burden in mice. Dietary supplementation with flavonoid composites attenuated obesity and continuous delivery of the catabolite 4-hydroxyphenylacetic acid was sufficient to reverse hepatic steatosis. We showed that this anti-steatotic effect is associated with the activation of AMP-activated protein kinase a. Analysis of healthy human gut metagenomes revealed that under one percent of individuals contains a complete flavonol catabolic pathway, underscoring the rarity of this process in people. Our study will impact the design of dietary and probiotic interventions to complement traditional cardiometabolic treatment strategies.