Scytosiphon lomentaria Fucoidan Ameliorates Glucose and Lipid Abnormalities via Modulation of the Microbiota–Gut–Liver/Pancreas Axis: Insights from Multiomics Analysis

Fucoidan (FUC2), purified from Scytosiphon lomentaria, improved glucose and lipid metabolism in mice by modulating the gut–liver/pancreas axis through structural remodeling of the gut microbiota. Structural characterization revealed that FUC2 is a homogeneous acidic heteropolysaccharide mainly composed of fucose-, mannose-, and galactose-rich regions with possible glycosidic linkages. Mice experiments demonstrated that FUC2 attenuated insulin resistance and oxidative stress by activating the AMPK and Nrf2 signaling pathways. FUC2 administration significantly increased the abundance of beneficial bacteria, including Bacteroides, Faecalibaculum, and Bifidobacterium, and consequently altered levels of microbial-derived metabolites such as short-chain fatty acids, bile acids, and amino acids. The metabolic benefits were mediated through the bile acid–FXR–FGF15 axis and were further validated by a Bacteroides supplementation experiment. These results suggest that FUC2 may serve as a potential prebiotic agent for ameliorating metabolic disorders via microbiota-dependent mechanisms.