Abstract / Summary
Hyperuricemia is a common metabolic disorder associated with gout, chronic kidney disease, and cardiovascular complications. Despite the availability of urate-lowering therapies such as xanthine oxidase inhibitors, their long-term use may be constrained in some patients due to adverse effects, contraindications, or suboptimal adherence. In this context, probiotics have emerged as promising functional food components with potential roles in metabolic regulation and disease prevention. This review comprehensively examines synergistic strategies for uric acid reduction, focusing on the combined use of probiotics, prebiotics, synbiotics, and postbiotics. Special attention is given to emerging approaches, such as microbial co-culture systems, including yeast–lactic acid bacteria combinations, as innovative sources of bioactive metabolites with enhanced functional potential. Preclinical evidence suggests that probiotic-based interventions may influence uric acid homeostasis through several interconnected pathways, including modulation of gut microbiota composition, purine metabolism and xanthine oxidase activity, regulation of urate transporters such as URAT1 and ABCG2, and attenuation of oxidative stress and inflammatory signaling. Additionally, experimental studies indicate that synergistic formulations may support intestinal barrier function and metabolic cross-feeding, particularly through postbiotic and co-culture-derived metabolites. However, most of the available evidence remains preclinical, while human clinical studies are still limited, heterogeneous in design, and insufficient to establish comparative therapeutic efficacy. Accordingly, probiotic-, postbiotic-, and co-culture-based approaches should currently be regarded as emerging adjunctive strategies with potential multitarget effects rather than alternatives to established urate-lowering therapies. Future studies should include well-designed clinical trials, mechanistic studies in human models, and the development of personalized and next-generation probiotic formulations to support clinical translation.