Fucoidan Supplementation Relieved Kidney Injury and Modulated Intestinal Homeostasis in Hyperuricemia Mice

Hyperuricemia is a metabolic disease characterized by an excessively increased level of uric acid (UA) in the blood, with an increasing prevalence and often associated with kidney damage. Gut microbiota and endotoxins of gut origin are key mediators in the gut–kidney axis that can cause renal impairment. The study was to reveal the protective effects of fucoidan on renal injury caused by hyperuricemia. The hyperuricemia model was established in C57BL/6J mice. After 10 weeks of fucoidan supplementation, we found that the levels of serum UA and creatinine were reduced, and the levels of renal tumor necrosis factor α, interleukin-18 (IL-18), IL-6, and interleukin-1β (IL-1β) were also decreased. Fucoidan inhibited the expressions of phosphorylated NF-κB p65, NLRP3, and activated caspase-1 in the kidneys. Fucoidan also regulated the expressions of Bcl-2 family proteins and decreased the activation of caspase-3, thereby exerting antiapoptotic effect. In addition, fucoidan could reduce the expressions of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) proteins, thereby promoting the excretion of UA from the kidneys. Moreover, the protective effect of fucoidan on renal injury may be related to maintaining intestinal homeostasis. Fucoidan reduced serum lipopolysaccharide and improved the intestinal mucosal barrier function. Fucoidan decreased the abundances of Blautia, Muribaculaceae, and Dubosiella, and increased the abundances of Lactobacillus. High-dose fucoidan supplementation increased the content of butyric acid and enhanced the expression of ATP binding box transporter G2 (ABCG2) via the AMPK/AKT/CREB pathway in ileum. Conclusion: Fucoidan could protect against hyperuricemia-induced renal injury by inhibiting renal inflammation and apoptosis and modulating intestinal homeostasis in hyperuricemia mice.