Gut microbiota-mediated uric acid metabolism: Novel insights for developing urate-lowering and anti-gout medications.

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.