Gut microbiota-mediated uric acid metabolism: Novel insights for developing urate-lowering and anti-gout medications
- 1Department of Medicinal Chemistry, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shandong Key Laboratory of Druggability Optimization and Evaluation for Lead Compounds, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong, 250012, China
- 2NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China
- 3NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; Corresponding author.
Abstract
Hyperuricemia, caused by purine metabolism dysfunction and impaired uric acid excretion, is increasing in prevalence globally. Current urate-lowering drugs have limitations in safety and applicability. The gut, which is central to uric acid production and excretion, hosts microbiota closely linked to uric acid metabolism and gout-related inflammation. This paper summarizes advances from PubMed and CNKI (2012–March 2026) on microbiota-mediated regulation of uric acid metabolism and gout. Gut microbiota promote hyperuricemia and gout via multiple mechanisms: regulating purine metabolism and uric acid production, degrading urate, modulating intestinal urate transport, and activating inflammatory pathways. We further classify microbiota-targeted urate-lowering interventions into four categories: (i) microbial metabolites and functional strains, (ii) microbiota-modulating natural products, (iii) microbiota-utilizing polysaccharides, and (iv) bioactive peptides. These strategies have unique advantages including high intestinal exposure, microbiota responsiveness, structural diversity, and multi-pathway regulation potential, acting via key axes such as microbiota–PPARγ–ABCG2 and TLR4/NF-κB–NLRP3. By targeting systemic regulation instead of simple transporter inhibition, they fill critical gaps in current therapy. From a medicinal chemistry perspective, these molecules are promising prototype templates for safer, more effective anti-hyperuricemic and anti-gout drugs.
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BibTeX
@article{jiang2026microbiotamediated,
title = {{Gut microbiota-mediated uric acid metabolism: Novel insights for developing urate-lowering and anti-gout medications}},
author = {Yuxin Jiang and Xiaoyu Shi and Qian Yang and Jianxin Pang and Peng Zhan and Shujing Xu and Ting Wu},
journal = {Pharmaceutical Science Advances},
year = {2026},
month = nov,
doi = {10.1016/j.pscia.2026.100148},
url = {https://doi.org/10.1016/j.pscia.2026.100148},
note = {CC BY},
}
RIS
TY - JOUR
TI - Gut microbiota-mediated uric acid metabolism: Novel insights for developing urate-lowering and anti-gout medications
AU - Yuxin Jiang
AU - Xiaoyu Shi
AU - Qian Yang
AU - Jianxin Pang
AU - Peng Zhan
AU - Shujing Xu
AU - Ting Wu
PY - 2026
DA - 2026/11/06
JO - Pharmaceutical Science Advances
DO - 10.1016/j.pscia.2026.100148
UR - https://doi.org/10.1016/j.pscia.2026.100148
AB - Hyperuricemia, caused by purine metabolism dysfunction and impaired uric acid excretion, is increasing in prevalence globally. Current urate-lowering drugs have limitations in safety and applicability. The gut, which is central to uric acid production and excretion, hosts microbiota closely linked to uric acid metabolism and gout-related inflammation. This paper summarizes advances from PubMed and CNKI (2012–March 2026) on microbiota-mediated regulation of uric acid metabolism and gout. Gut microbiota promote hyperuricemia and gout via multiple mechanisms: regulating purine metabolism and uric acid production, degrading urate, modulating intestinal urate transport, and activating inflammatory pathways. We further classify microbiota-targeted urate-lowering interventions into four categories: (i) microbial metabolites and functional strains, (ii) microbiota-modulating natural products, (iii) microbiota-utilizing polysaccharides, and (iv) bioactive peptides. These strategies have unique advantages including high intestinal exposure, microbiota responsiveness, structural diversity, and multi-pathway regulation potential, acting via key axes such as microbiota–PPARγ–ABCG2 and TLR4/NF-κB–NLRP3. By targeting systemic regulation instead of simple transporter inhibition, they fill critical gaps in current therapy. From a medicinal chemistry perspective, these molecules are promising prototype templates for safer, more effective anti-hyperuricemic and anti-gout drugs.
SN - 2773-2169
ER -