Fucoidan alleviates kidney fibrosis by shaping the gut microbiota and modulating tryptophan metabolism.

Chronic kidney disease (CKD) is a major global health burden, with renal fibrosis as the key pathological driver of disease progression. Fucoidan (FPS) is a sulfated polysaccharide from brown algae that has demonstrated renoprotective and anti-fibrotic properties. However, its metabolic and microbiota-related mechanisms remain unclear. Here, we evaluated the efficacy of FPS in a unilateral ureteral obstruction (UUO) mouse model, in which mice received oral FPS (100 or 200 mg kg-1 day-1) for 14 days. Kidney metabolomics and 16S rRNA sequencing of the gut microbiota were performed. As a result, UUO induced pronounced disturbances in tryptophan metabolism and marked gut microbial dysbiosis. FPS treatment attenuated renal fibrosis, normalized key tryptophan pathway intermediates and related metabolic enzymes in the kidneys, and partially restored the gut microbial composition. These results implicate the modulation of tryptophan metabolism and the gut microbiota in the anti-fibrotic effects of FPS, supporting its potential as a natural therapeutic candidate for renal fibrosis and CKD.