ArticleProceedings of the National Academy of Sciences of the United States of America2022
A gut microbial metabolite of dietary polyphenols reverses obesity-driven hepatic steatosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 66 citations in OpenAlex.
- Metabolome Profiling of Yokukansan in Preventing Postoperative Delirium in Elderly Cancer Patients: A Reverse Translational Study.Psychiatry and clinical neurosciences · 2025Trial
- Effects of healthy low-carbohydrate diet and time-restricted eating on weight and gut microbiome in adults with overweight or obesity: Feeding RCT.Cell reports. Medicine · 2024Trial
- Microbiota-derived 4-HPAA alleviates Crohn's disease by stabilizing SIRT1 and reprogramming macrophage immunometabolism.Apoptosis : an international journal on programmed cell death · 2026Article
- Phenylacetic Acid, a Gut Microbially Produced Metabolite, Reduces Atherosclerosis Burden and Impacts Host Lipid Homeostasis.Journal of the American Heart Association · 2026Article
- A microbial metabolite reduces alcohol-induced inflammation via dual modulation of NF-κB and Interferon pathway.bioRxiv : the preprint server for biology · 2026Article
- The Gut Microbiota-Polyphenol-NLRP3 Inflammasome Axis: A Key Regulatory Network Linking Diet to Chronic Inflammation.Nutrients · 2026Review
- Microbiome modulating remedies for chronic diseases: a review of current interventions and future directions.Inflammopharmacology · 2026Review
- The skin microbiota drives cutaneous immune checkpoint inhibitor toxicity in genetically susceptible mice.Cell host & microbe · 2026Article
- Gut microbiota-derived metabolites as immune modulators in aging and age-related chronic inflammatory diseases.Ageing research reviews · 2026Review
- Variation in Microbiome Composition and Faecal Metabolites Are Associated With Differential Susceptibility to DSS-Induced Colitis.Immunology · 2026Article
- Gut microbe-derivedProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Bioengineering Interventions to Enhance the Capacity of the Gut Microbiota in Controlling Food Allergies.Life (Basel, Switzerland) · 2026Review
- Paulobutalipin, a Lipid Accumulation Inhibitor from aJournal of natural products · 2026Article
- Epigallocatechin gallate prevents and alleviates type 2 diabetes mellitus (T2DM) through gut microbiota and multi-organ interactions in Wistar healthy rats and GK T2DM rats.Journal of advanced research · 2026Article
- Unveiling the Metabolic Fingerprint of Occupational Exposure in Ceramic Manufactory Workers.Toxics · 2026Article
- The gut-liver axis: microbial mechanisms and therapeutic implications in MAFLD.Frontiers in cellular and infection microbiology · 2026Review
- Gut microbial metabolites of amino acids in liver diseases.Gut microbes · 2025Review
- Bidirectional microbial regulation by tyrosine metabolism enhances palmatine-mediated colitis protection.Gut microbes · 2025Article
- The diet-derived gut microbial metabolite 3-phenylpropionic acid reverses insulin resistance and obesity-associated metabolic dysfunction.Molecular metabolism · 2025Article
- Gut microbiota-derived 4-hydroxyphenylacetic acid from resveratrol supplementation prevents obesity through SIRT1 signaling activation.Gut microbes · 2025Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
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 hinge, in part, on gut microbial metabolism. Specifically, we show that a single gut microbial flavonoid catabolite, 4-hydroxyphenylacetic acid (4-HPAA), is sufficient to reduce diet-induced cardiometabolic disease (CMD) burden in mice. The addition of flavonoids to a high fat diet heightened the levels of 4-HPAA within the portal plasma and attenuated obesity, and continuous delivery of 4-HPAA was sufficient to reverse hepatic steatosis. The antisteatotic effect was shown to be associated with the activation of AMP-activated protein kinase α (AMPKα). In a large survey of healthy human gut metagenomes, just over one percent contained homologs of all four characterized bacterial genes required to catabolize flavonols into 4-HPAA. Our results demonstrate the gut microbial contribution to the metabolic benefits associated with flavonoid consumption and underscore the rarity of this process in human gut microbial communities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.