Threee Lactic Acid Bacteria Capable of Degrading Purine Nucleosides and Inhibiting Xanthine Oxidase and Their Combination Alleviate Hyperuricemia and Renal Inflammatory Responses Associated with AMPK/TLR4/NF-κB/NLRP3 Signaling in Mice

Hyperuricemia (HUA), a metabolic disorder strongly associated with gout and chronic kidney disease, has emerged as a target for probiotic-based complementary interventions. Three newly isolated lactic acid bacteria (LAB) strains were evaluated individually and in combination for their modulatory effects on HUA progression and renal inflammatory responses associated with the AMPK/TLR4/NF-κB/NLRP3 signaling axis. The purine nucleoside-degrading capacity and xanthine oxidase (XOD) inhibitory activity were characterized in vitro, followed by a 21-day oral intervention (n = 6) in a yeast extract and potassium oxonate-induced mouse model of HUA. Hepatic and renal cytokine concentrations and renal pathway-related proteins were quantified by ELISA, with the corresponding gene expressions analyzed by RT-qPCR. All three strains degraded purine nucleosides (up to 99.28 ± 1.25% within 120 min) and inhibited XOD activity (up to 61.55 ± 1.33%) in vitro. Single and combined strains significantly lowered serum uric acid (UA) and hepatic and serum XOD activity in vivo, with dose-related trends. The high-dose combination reduced serum UA by 41.39 ± 1.73% versus the model group. Hepatic and renal pro-inflammatory cytokines were downregulated, and IL-10 was upregulated, accompanied by modulation of renal AMPK/TLR4/NF-κB/NLRP3-related markers. These strains, especially their combination, represent promising HUA probiotic candidates for further preclinical validation.