Hyperuricemia is a critical threat to human health, and conventional medical treatment only aims to treat acute gouty arthritis. Purine diet-mediated chronic hyperuricemia and related syndromes are neglected in clinical therapeutics. In this study, the prevention ability of Lacticaseibacillus rhamnosus Fmb14, screened from Chinese yogurt, was evaluated in chronic purine-induced hyperuricemia (CPH) mice. After 12 weeks of Fmb14 administration, serum uric acid (SUA) in CPH mice decreased by 36.8 %, from 179.1 to 113.2 µmol/L, and the mortality rate decreased from 30 % to 10 %. The prevention role of Fmb14 in CPH was further investigated, and the reduction of uric acid by Fmb14 was attributed to the reduction of XOD (xanthine oxidase) in the liver and URAT1 in the kidney, as well the promotion of ABCG2 in the colon. Fmb14 administration Increased ZO-1 and Occludin expression in the colon and decreased fibrosis degree in the kidney indicated that Fmb14 administration had preventive effects through the gut-kidney axis in CPH. In specific, Fmb14 administration upregulated the diversity of gut microbiota, increased short-chain fatty acids (SCFA) by 35 % in colon materials and alleviated the inflammatory response by reducing biomarkers levels of IL-1β, IL-18 and TNF-α at 11.6 %, 21.7 % and 26.5 % in serum, compared to CPH group, respectively. Additionally, 16 S rRNA sequencing showed 31.5 % upregulation of Prevotella, 20.5 % and 21.6 % downregulation of Ruminococcus and Suterella at the genus level, which may be a new gut microbial marker in hyperuricemia. In conclusion, Fmb14 ameliorated CPH through the gut-kidney axis, suggesting a new strategy to prevent hyperuricemia.