Abstract
The molecular mechanisms by which dietary fruits and vegetables confer cardiometabolic benefits remain poorly understood. Historically, these beneficial properties have been attributed to the antioxidant activity of flavonoids. Here, we reveal that the host metabolic benefits associated with flavonoid consumption actually hinge on gut microbial metabolism. We show that a single gut microbial flavonoid catabolite is sufficient to reduce diet-induced cardiometabolic disease burden in mice. Dietary supplementation with elderberry extract attenuated obesity and continuous delivery of the catabolite 4-hydroxphenylacetic acid was sufficient to reverse hepatic steatosis. Analysis of human gut metagenomes revealed that under one percent contains a flavonol catabolic pathway, underscoring the rarity of this process. Our study will impact the design of dietary and probiotic interventions to complement traditional cardiometabolic treatment strategies.
One-Sentence Summary Select gut microbes can metabolize flavonoids from a fruit and vegetable diet to monophenolic acids, which improve fatty liver disease.
Competing Interest Statement
JC is a Scientific Advisor for Seed Health, Inc. ZW and SLH report being named as co-inventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics. SLH reports being a paid consultant for Procter & Gamble, and Zehna Therapeutics, having received research funds from Procter & Gamble, Roche Diagnostics and Zehna therapeutics, and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland Heart Lab, a fully owned subsidiary of Quest Diagnostics, and Procter & Gamble. The other authors declare they have no competing interests.
