Fuc‐S, a New Degraded Polysaccharide From Fucoidan, Alleviates Type 2 Diabetes‐Associated Liver Injury Through Modulating Gut Microbiota

ABSTRACT Type 2 diabetes mellitus (T2DM) is frequently associated with liver injury. This study examines the therapeutic potential of Fucus vesiculosus ‐derived low‐molecular‐weight fucoidan (Fuc‐S) in mitigating T2DM‐related hepatic damage. In STZ/HFD‐induced diabetic mice, Fuc‐S treatment (100 or 200 mg/kg, 5 weeks) significantly improved glucose tolerance, lipid metabolism, and liver function, while reducing hepatic steatosis and serum ALT/AST levels. Fuc‐S enhanced hepatic antioxidant defenses, increasing SOD, CAT, and GSH‐Px activity while decreasing MDA levels. Gut microbiota analysis showed that Fuc‐S promoted the growth of beneficial bacteria ( Bacteroides acidifaciens ) and elevated fecal short‐chain fatty acids (SCFAs), such as acetate, propionate, and butyrate. Furthermore, Fuc‐S reinforced intestinal barrier integrity by upregulating tight junction proteins (ZO‐1 and occludin). These results indicate that Fuc‐S alleviates T2DM‐induced liver injury by modulating the gut microbiota‐SCFA‐liver axis, thereby reducing oxidative stress and inflammation. The study suggests Fuc‐S as a promising dietary intervention for T2DM, acting through multi‐target microbiota‐metabolite interactions.