2′-Fucosyllactose evokes colonization of <i>Alloprevotella</i> and alleviates renal injury in hyperuricemia mice

Hyperuricemia (HUA) is a metabolic disease characterized by the overproduction of uric acid (UA) in the blood, with an increasing prevalence of associated renal injury. Intestinal microbiota and its associated metabolites are important mediators in the gut-kidney axis that can induce renal impairment. This study investigated the effect of 2'-fucosyllactose (2'FL) on HUA and its underlying mechanisms. In a hyperuricemic <i>Caenorhabditis elegans</i> model, 2'FL reduced the xanthine-induced UA levels and oxidative stress. In a HUA mice model induced with potassium oxonate and UA, 2'FL intervention (200 mg per kg body weight per d) improved UA metabolism and decreased the serum UA concentration, xanthine oxidase activity, blood urea nitrogen, and creatinine levels. 2'FL also alleviated renal injury, inflammatory response and oxidative stress, as evidenced by the reduced lipopolysaccharide, interleukin-6, and malondialdehyde levels and myeloperoxidase activity and increased interleukin-10 level and total antioxidant capacity. 2'FL enhanced renal UA excretion by upregulating ATP-binding cassette subfamily G member 2 (ABCG2) expression and downregulating urate transporter 1 (URAT1) expression. It inhibited renal ferroptosis by restoring the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) pathway and alleviated renal injury. In the gut, 2'FL protected the intestinal barrier, increased fecal short-chain fatty acids, and modulated intestinal microbiota composition. In particular, it reversed the HUA-induced changes in the <i>Firmicutes</i>/<i>Bacteroidetes</i> ratio and affected the abundance of certain genera correlated with UA metabolism. These findings suggest that 2'FL is a potential natural agent for HUA treatment with multiple beneficial effects on metabolism, renal function, and gut microbiota.