Fucoidan attenuates hyperuricemia and renal inflammation in association with gut microbiota remodeling and enrichment of Lactobacillus plantarum.

Fucoidan has shown potential for the management of hyperuricemia (HUA), although its underlying mechanisms remain poorly understood. In this study, fucoidan from Undaria pinnatifida was fractionated, and the 0.8 M NaCl-eluted fraction (UPF-8) was evaluated in a mouse model of HUA. UPF-8 reduced serum uric acid, blood urea nitrogen, and creatinine levels, decreased adenosine deaminase and xanthine oxidase activities, and alleviated renal injury. These effects were accompanied by changes in serum metabolites related to purine and amino acid metabolism and the TCA cycle, improved intestinal barrier integrity, and remodeling of the gut microbiota, particularly an increase in Lactobacillus abundance. In vitro experiments indicated that the tested Lactobacillus strains did not directly utilize UPF-8, whereas their growth was enhanced in the presence of UPF-8-fermenting fecal microbial community, suggesting possible indirect microbial or metabolic interactions. Lactobacillus plantarum (LP) reproduced several of the biochemical, metabolic, and renal improvements observed following UPF-8 treatment. LP administration was associated with changes in renal GLUT9 and renal/colonic ABCG2 expression and reduced TLR4/NLRP3-associated inflammatory signaling. On the whole, UPF-8 alleviated HUA-associated abnormalities in association with gut microbiota remodeling and improvements in intestinal, metabolic, and renal homeostasis, supporting its potential as a microbiota-directed dietary intervention for HUA.