Abstract
Non-alcoholic steatohepatitis (NASH) is a progressive liver disease lacking effective treatment. This study investigated 2'-Fucosyllactose (2'-FL) for its therapeutic potential. In vitro, 2'-FL reduced lipid accumulation, oxidative stress, and inflammation in Hepa1-6 cells. In a NASH mouse model, 2'-FL alleviated key disease features: hepatic steatosis, inflammation, and oxidative stress. Furthermore, 2'-FL intervention reversed NASH-associated gut microbiota dysbiosis, specifically by increasing Bacteroidota and decreasing Firmicutes at the phylum level. Fecal microbiota transplantation (FMT) validated the role of gut microbiota in these effects. The findings indicate that 2'-FL ameliorates NASH by remodeling the gut microbiota, thereby reducing endotoxemia and improving lipid metabolism. This suggests 2'-FL as a promising dietary intervention for metabolic liver diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-025-02034-3.