RT Journal Article
SR Electronic
T1 A gut microbial metabolite of dietary polyphenols reverses obesity-driven hepatic steatosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.16.460661
DO 10.1101/2021.09.16.460661
A1 Lucas J. Osborn
A1 Karlee Schultz
A1 William Massey
A1 Beckey DeLucia
A1 Ibrahim Choucair
A1 Venkateshwari Varadharajan
A1 Kevin Fung
A1 Anthony J. Horak III
A1 Danny Orabi
A1 Ina Nemet
A1 Laura E. Nagy
A1 Zeneng Wang
A1 Daniela S. Allende
A1 Naseer Sangwan
A1 Adeline M. Hajjar
A1 Christine McDonald
A1 Philip P. Ahern
A1 Stanley L. Hazen
A1 J. Mark Brown
A1 Jan Claesen
YR 2021
UL http://biorxiv.org/content/early/2021/09/16/2021.09.16.460661.abstract
AB 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 StatementJC 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.