Min Wei, Yingsheng Hu, Xiaoxian Li, Xingyi Long, Zhihong Zhang, Xueying Tao, Hequn Wei
Background: Hyperuricemia (HUA) is associated with excessive uric acid (UA) production, impaired renal excretion, and gut microbial dysbiosis. This study aims to systematically evaluate the alleviating effects of exopolysaccharide (EPS04) derived from Lactiplantibacillus plantarum WLPL04 on HUA. Methods: The study employed both in vitro HK-2 cells and in vivo animal studies in HUA mice. Key methods included assessing xanthine oxidase (XOD) activity and reactive oxygen species (ROS) production in vitro and measuring serum UA levels, renal function parameters, XOD activity, and gene expression in vivo. Additionally, 16S rRNA sequencing was used to analyze gut microbiota composition. Results: EPS04 reduced UA production in HK-2 cells by inhibiting XOD activity and downregulating its gene expression while also decreasing XOD-derived ROS. EPS04 significantly lowered serum UA levels and attenuated renal injury in HUA mice. Hepatic XOD expression and activity were downregulated, reducing UA production, while UA excretion was enhanced through upregulation of renal ABCG2 expression. Furthermore, EPS04 increased gut microbiota α-diversity, restored the Bacteroidota/Firmicutes ratio, and enriched beneficial taxa, including Akkermansia and Dubosiella. Conclusions: EPS04 alleviates HUA through inhibition of XOD activity, upregulation of renal ABCG2 expression, and modulation of gut microbiota, suggesting its potential as a nutraceutical biopolymer for dietary management of HUA and related metabolic disorders.