Edible dock protein ameliorates hyperuricemia in mice: A multi-omics analysis implicating the gut–kidney axis

Background: Hyperuricemia (HUA) is caused by purine metabolism dysregulation or impaired uric acid (UA) excretion. Its global prevalence has increased, particularly among younger populations. Edible dock protein (EDP) possesses bioactivities, including hypoglycemic, antihypertensive, anti-inflammatory, and antioxidant effects; however, its UA-lowering and renoprotective mechanisms remain unclear. Methods: We evaluated EDP's therapeutic efficacy in an adenine-and potassium oxazolate-induced HUA mouse model using serum metabolomics, fecal 16S rRNA sequencing, and renal transcriptome analyses. Results: EDP significantly reduced elevated serum UA, creatinine, and urea nitrogen induced by adenine and potassium oxazolate, ameliorated renal tissue injury, and restored gut microbiota balance. EDP corrected adenine and potassium oxazolate-induced lipid and amino acid metabolism abnormalities, thereby alleviating oxidative stress and inflammatory responses. EDP suppressed HUA-induced immune and inflammatory pathways and restored metabolic and oxidative homeostasis. Conclusion: EDP has established a network connecting gut microbiota, lipid metabolism and kidney inflammation to alleviate HUA. These findings reveal a novel integrative mechanism for EDP's action and support its potential as a dietary strategy for HUA management. • Two major protein sequences of EDP were identified, providing structural insight into its bioactive properties. • EDP relieves hyperuricemia and renal injury in mice. • EDP regulates the intestinal microenvironment, increasing beneficial bacteria while reducing harmful bacteria. • EDP imparts beneficial effects on the renal microenvironment by regulating purine and amino acid metabolism. • It provides a solid theoretical foundation for the development of novel food ingredients.