Prevotella copri alleviates hyperuricemia via uricolysis and gut microbiota reconstruction

Abstract

Despite the therapeutic promise of uric acid-metabolizing microbes for hyperuricemia, their application is hindered by the scarcity of highly efficacious strains. To identify uric acid-metabolizing microbes, we enriched gut microbiota from cynomolgus monkeys under uric acid-supplemented conditions. This selection increased the abundance of Prevotellaceae_UCG-001 and norank_f_Prevotellaceae, implicating Prevotella species as key uric acid degraders. In vitro validation confirmed efficient uric acid consumption by two new Prevotella isolates and the reference strain Prevotella copri DSM 18205 (P. copri). Oral administration of P. copri in hyperuricemic mice reduced uric acid levels in serum and kidney tissues and alleviated renal fibrosis by suppressing the TGF-{beta}/Smad pathway and downstream fibrogenic genes. Moreover, P. copri administration restored the depleted population of Faecalibaculum, and further assays demonstrated that Faecalibaculum rodentium directly metabolizes uric acid. Collectively, P. copri alleviates hyperuricemia via a dual mechanism: direct uric acid catabolism and enrichment of commensal uric acid-consuming bacteria. These findings establish P. copri as a promising live biotherapeutic agent for hyperuricemia and highlight microbial collaboration as a therapeutic strategy for metabolic diseases.