Abstract Hyperuricemia (HUA) is a metabolic disease caused by the disorder of uric acid (UA) metabolism. In recent years, it has been found that fucoidan (FC) has anti-HUA effect, but the mechanism is still lack of systematic research. The aim of this study was to investigate the mechanism of FC on HUA through UA metabolism and intestinal homeostasis. Based on PMP-derived ultra performance liquid chromatography analysis, FC was identified as a sulfated polysaccharide composed of galactose, mannose, trace amounts of mannuronic acid, and xylose. The HUA mouse model was induced by a high-purine diet and potassium oxonate. We found that FC significantly ameliorated renal inflammation and injury and reduce serum UA level in HUA mice. Furthermore, FC intervention modulated UA metabolism by regulating purine metabolic enzyme activity and the expression of UA transporters in the kidney and intestine. It also protected the intestinal tract from damage by upregulating the expression of gut barrier-associated genes, including ZO-1, Claudin, Occludin, and MUC2. 16S rRNA sequencing and targeted metabolomics analysis further revealed that FC administration altered the composition of the gut microbiota, increasing the abundance of beneficial bacteria such as Muribaculum, Alloprevotella, ClostridiaUCG-014, and Rikenella, while decreasing the abundance of harmful bacteria such as Parabacteroides, Enterorhabdus, and Muribaculaceae. Meanwhile, FC reversed the reduction in short-chain fatty acid levels caused by HUA. In sum, FC is a natural UA-lowering active substance with multiple targets and pathways. This study provides new evidence supporting the potential of FC as a dietary supplement for patients with HUA.
Meng et al. (Mon,) studied this question.