Low molecular fucoidan alleviated alcohol-induced liver injury in BALB/c mice by regulating the gut microbiota-bile acid-liver axis.

Fucoidan has attracted significant attention owing to its remarkable bioactivities, but the effect of molecular weight (Mw) on its activities in the context of alcoholic liver diseases (ALD) is poorly understood. In this study, low Mw fucoidan (OSLF) was prepared, and its protective effect against alcohol-induced liver injury was assessed in a mouse model. OSLF increased weight gain and colon length, improved lipid disorders, and reduced oxidative stress in mice exposed to alcohol, alleviating liver injury. OSLF alleviated inflammation in the liver by inhibiting alcohol-activated NF-κB and MAPK pathways. The underlying mechanism can be attributed to the improvement of alcohol-induced dysbiosis of the gut microbiota, including a decrease in Proteobacteria and Bacteroidetes and an increase in microbiota diversity, as well as the abundances of Parabacteroides, Bacteroides, and Faecalibaculum. Metabolomics results showed that OSLF improved alcohol-induced abnormalities of microbiota metabolites, primarily involving amino acid metabolism and short chain fatty acids production. In addition, OSLF ameliorated bile acid metabolism in the gut and regulated the expression of bile acid-associated genes in the liver, affecting bile acid synthesis, regulation, and transport. It suggested that OSLF had the potential for the management of ALD by regulating the gut microbiota-bile acid-liver axis.