Complex interactions of gut-derived short-chain fatty acids in hyperuricemia and gout pathophysiology

Hyperuricemia is a common metabolic disorder associated with gout, kidney injury, cardiovascular disease, and chronic low-grade inflammation. Increasing evidence indicates that abnormalities in intestinal uric acid handling and gut microbial metabolism contribute substantially to systemic urate imbalance, particularly when renal excretion is impaired. Among microbiota-derived metabolites, short-chain fatty acids (SCFAs) have emerged as key regulators linking gut microbial ecology with uric acid metabolism through coordinated effects on epithelial barrier integrity, inflammatory signaling, and urate transport. Growing interest in prebiotics and probiotics has further highlighted the therapeutic potential of targeting SCFAs production as a complementary strategy to traditional urate-lowering drugs. Given that hyperuricemia is the primary pathogenic precursor to gout, this review also examines the role of SCFAs in modulating gout-associated inflammation. This review integrates current findings on the microbiota-SCFA-urate axis and outlines how SCFA-centered gut modulation may provide a viable framework for managing hyperuricemia and gout.