关键词: 动物双歧杆菌乳亚种；高尿酸血症；黄嘌呤氧化酶；组织损伤；肠道菌群

Abstract: Objective: To explore the potential molecular mechanism by which Bifidobacterium animalis subsp. lactis YRK-12 alleviates hyperuricemia (HUA) induced by combined oral administration of inosine, guanosine and potassium oxonate in mice. Methods: All mice were randomly divided into three groups: control, HUA model (MOD), and B. animalis subsp. lactis YRK-12 intervention (YRK-12). The administration period lasted 21 days. Subsequently, serum biochemical indicators, liver xanthine oxidase (XOD) activity, histopathological sections, the expression of urate transporter genes and inflammatory genes, and changes in the intestinal flora were measured. Results: B. animalis subsp. lactis YRK-12 intervention significantly reduced serum uric acid levels by 35.7% and improved renal function indicators. YRK-12 significantly reduced liver XOD activity by 32.2% and decreased ileum XOD expression levels; the expression levels of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) in the kidney were significantly down-regulated by 44.8% and 25.7%, respectively. The expression levels of ATP-binding cassette subfamily G member 2 (ABCG2) in the kidney and colon were significantly up-regulated by 22.0% and 20.6%, respectively. Meanwhile, YRK-12 significantly inhibited the nuclear factor kappa-B/NOD-like receptor family pyrin domain containing 3 (NF-κB/NLRP3) signaling pathway, reducing the expression levels of NF-κB and NLRP3 in the kidney by 40.4% and 31.4%, respectively. It also increased the abundance of Actinomycetota and short-chain fatty acid-producing bacteria (such as Alistipes putredinis and Suilimivivens aceti), thereby improving intestinal microbial dysbiosis. Conclusion: B. animalis subsp. lactis YRK-12 can alleviate HUA through multiple pathways, including regulating uric acid synthesis and excretion, reducing tissue inflammation, and modulating the intestinal flora. This finding provides a theoretical basis and experimental support for the development of probiotic products to prevent and alleviate HUA.

Key words: Bifidobacterium animalis subsp. lactis; hyperuricemia; xanthine oxidase; tissue damage; intestinal microflora