Resveratrol Ameliorates Hyperuricemia in Association with Remodeling of the Gut Microbiota-Metabolism Axis: An Integrated 16S rDNA Sequencing and Fecal Metabolomics Study.
4 affiliations
- 1Key Laboratory of Development and Utilization of Food and Medicinal Resources, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China.
- 2Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China.
- 3Yunnan Key Laboratory of Precision Nutrition and Personalized Food Manufacturing, Yunnan Agricultural University, Kunming 650201, China.
- 4College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China.
Abstract
Hyperuricemia (HUA) is a chronic metabolic disorder whose prevalence continues to rise, whereas available urate-lowering drugs are limited by safety and tolerability concerns. Resveratrol (Res) exhibits urate-lowering activity, but its oral bioavailability is below 1%, prompting investigation of its potential interactions with the gut microbiota. Here, hyperuricemic mice induced by potassium oxonate plus high-fructose intake were treated with Res (20, 40, or 80 mg/kg) or benzbromarone (20 mg/kg), and 16S rDNA sequencing, PICRUSt2 functional prediction, untargeted fecal metabolomics, and multi-omics network analysis were integrated to characterize the underlying mechanisms. Res (80 mg/kg) significantly lowered serum uric acid, inhibited xanthine oxidase and adenosine deaminase activities, improved renal injury, suppressed pro-inflammatory cytokines, and up-regulated colonic barrier genes with reduced serum lipopolysaccharide. Res normalized inflated microbial richness, restored Akkermansia abundance, and PICRUSt2 prediction indicated down-regulation of the microbial purine-metabolism gene families XOD/XDH and UOX by 29.4% and 85.9%, respectively. Metabolomics identified 41 shared differential metabolites including eicosanoid lipid mediators and glycerophospholipids. Multi-omics exploratory network analysis suggested Akkermansia as a potential hub node associated with microbial remodeling, eicosanoid modulation, and host urate phenotypes, which may represent a "urate-production suppression plus microbiota-metabolism axis regulation" mode of action, providing preclinical evidence for Res as a candidate dietary intervention against HUA.
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BibTeX
@article{wang2026resveratrol,
title = {{Resveratrol Ameliorates Hyperuricemia in Association with Remodeling of the Gut Microbiota-Metabolism Axis: An Integrated 16S rDNA Sequencing and Fecal Metabolomics Study.}},
author = {Yan Wang and Jing Xie and Zuoming Cao and Xiaoyu Gao and Zuoting Yang and Yang Tian and Jun Sheng and Lei Peng},
journal = {Foods (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/foods15203686},
url = {https://europepmc.org/article/MED/42940323},
note = {CC BY},
}
RIS
TY - JOUR
TI - Resveratrol Ameliorates Hyperuricemia in Association with Remodeling of the Gut Microbiota-Metabolism Axis: An Integrated 16S rDNA Sequencing and Fecal Metabolomics Study.
AU - Yan Wang
AU - Jing Xie
AU - Zuoming Cao
AU - Xiaoyu Gao
AU - Zuoting Yang
AU - Yang Tian
AU - Jun Sheng
AU - Lei Peng
PY - 2026
DA - 2026/10/16
JO - Foods (Basel, Switzerland)
DO - 10.3390/foods15203686
UR - https://europepmc.org/article/MED/42940323
AB - Hyperuricemia (HUA) is a chronic metabolic disorder whose prevalence continues to rise, whereas available urate-lowering drugs are limited by safety and tolerability concerns. Resveratrol (Res) exhibits urate-lowering activity, but its oral bioavailability is below 1%, prompting investigation of its potential interactions with the gut microbiota. Here, hyperuricemic mice induced by potassium oxonate plus high-fructose intake were treated with Res (20, 40, or 80 mg/kg) or benzbromarone (20 mg/kg), and 16S rDNA sequencing, PICRUSt2 functional prediction, untargeted fecal metabolomics, and multi-omics network analysis were integrated to characterize the underlying mechanisms. Res (80 mg/kg) significantly lowered serum uric acid, inhibited xanthine oxidase and adenosine deaminase activities, improved renal injury, suppressed pro-inflammatory cytokines, and up-regulated colonic barrier genes with reduced serum lipopolysaccharide. Res normalized inflated microbial richness, restored Akkermansia abundance, and PICRUSt2 prediction indicated down-regulation of the microbial purine-metabolism gene families XOD/XDH and UOX by 29.4% and 85.9%, respectively. Metabolomics identified 41 shared differential metabolites including eicosanoid lipid mediators and glycerophospholipids. Multi-omics exploratory network analysis suggested Akkermansia as a potential hub node associated with microbial remodeling, eicosanoid modulation, and host urate phenotypes, which may represent a "urate-production suppression plus microbiota-metabolism axis regulation" mode of action, providing preclinical evidence for Res as a candidate dietary intervention against HUA.
SN - 2304-8158
ER -