The roles of gut microbiota and their metabolites in uric acid–related metabolic diseases: mechanisms and therapeutic targets

Gut microbiota and their metabolites play a central regulatory role in uric-acid–related metabolic diseases, serving as a crucial interface linking purine metabolism with host inflammatory responses. This review synthesizes current evidence on microbial community alterations, metabolic functional shifts, and receptor-mediated signaling mechanisms in hyperuricemia, gout, and uric acid nephropathy. Studies demonstrate that gut microbes can directly degrade purine substrates, modulate uric acid transporters and metabolic enzyme activity, and regulate host pathways through metabolites such as short-chain fatty acids, bile acids, and indole derivatives acting on receptors including GPR41 and GPR43. These interactions collectively shape the dynamic balance between uric acid production and excretion. Probiotic and prebiotic interventions, such as Lactobacillus fermentum GR-3, Lactobacillus johnsonii YH1136, and Lactobacillus gasseri PA-3, effectively improve uric acid dysregulation via the gut–kidney and gut–liver axes, underscoring their therapeutic potential. In parallel, emerging metabolite- and receptor-targeted strategies provide new opportunities for precision intervention in uric-acid–related metabolic disorders. Future work should emphasize mechanistic causality and individualized host–microbe interactions within the microbe–metabolite–host signaling network to support clinical translation of microbiota-based therapies.