Interactions between serum uric acid and gut microbiota: implications for metabolic health

Serum uric acid (SUA), the end product of purine metabolism, is a known risk factor for developing gout; however, recent evidence suggests its broader role in metabolic disorders. The gut microbiota, a complex microbial ecosystem, plays a crucial role in influencing purine metabolism and intestinal uric acid (UA) excretion. Recent findings have uncovered a two-way relationship: certain microbes can metabolize purines and UA, while elevated UA can reduce microbial diversity, alter the production of SCFAs, and compromise intestinal barrier function. These interactions are linked to obesity, insulin resistance, T2D, NAFLD, and CVD, connecting purine metabolism with overall metabolic health. This review synthesizes current experimental and clinical evidence on SUA-microbiota interactions, with an emphasis on microbial enzymes, host urate transporters, and microbial metabolites, including bile acids and SCFAs. It also discusses therapeutic implications, spanning urate-lowering drugs to microbiota-targeted strategies, including probiotics, prebiotics, and dietary modulation. Despite progress, significant gaps remain: most human studies are cross-sectional, microbial taxa influencing SUA remain inconsistent, and interindividual microbiome variability limits the translation of findings to personalized care. Future multi-omics and longitudinal approaches are necessary to elucidate causal pathways and identify biomarkers, ultimately informing innovative strategies for the prevention and treatment of metabolic diseases beyond gout.