Hyperuricemia: Gut-kidney axis connection, Mechanisms and applications for probiotic treatment, and future directions

Hyperuricemia, a metabolic disorder marked by dysregulated uric acid (UA) metabolism, significantly contributes to the development of various chronic diseases. The homeostatic control of UA, affected by genetic background, environmental cues, and gut microbial activity, is essential for preventing dysregulated serum UA levels. Evidence indicates that high-purine diets cause gut dysbiosis and increase intestinal permeability, enabling translocation of harmful metabolites into systemic circulation. This can provoke renal inflammation and impair UA excretion, exacerbating hyperuricemia (HUA). The gut and kidneys interact bidirectionally through the gut-kidney axis, which is influenced by gut microbiota and their metabolites. Probiotics have demonstrated potential in restoring gut-kidney axis function and modulating UA metabolism by regulating the levels of short-chain fatty acids, bile acids, proline, and tryptophan derivatives. Nonetheless, comprehensive reviews on probiotic interventions for hyperuricemia remain scarce. This review explores the intricate interplay among gut-kidney axis, gut microbiota and metabolites, UA metabolism, and HUA. It further outlines the role of probiotics in regulating gut microbiota and UA metabolism. Finally, probiotic strategies including direct supplementation, functional foods, synbiotics, and delivery systems are summarized for the management of HUA. Despite this promise, challenges in strain selection, dosage standardization, and industrial scalability must be addressed. Future research should aim to improve the stability of probiotic formulations and develop personalized microbiota interventions based on individual variables.