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

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.