Fecal microbiota transplantation alleviates steatosis and inflammation in high-fat and high-sugar diet-induced fatty liver in mice

Aim: To investigate whether fecal microbiota transplantation (FMT) could alleviate high-fat and high-sugar (HFCS) diet-induced metabolic dysfunction-associated fatty liver disease (MAFLD) in mice and explore potential mechanisms underlying gut microbiota modulation. Methods: A MAFLD mouse model was established by feeding mice a HFCS diet for 20 weeks, followed by an 8-week intervention with FMT or saline, continuing for a total of 28 weeks. Gut microbiota composition, serum biochemical markers, liver histopathology, and inflammatory cytokine expression were evaluated. Results: The HFCS diet induced significant changes in gut microbiota, including increased Firmicutes and decreased Bacteroidetes and Bifidobacterium. FMT partially restored microbiota composition to resemble that of control mice. Mice receiving FMT showed reduced body weight and a consistent trend toward improvement in serum alanine transaminase and total cholesterol levels, although these changes did not reach statistical significance. Liver histology showed amelioration of steatosis and inflammation, as evidenced by reduced MAFLD activity score and decreased intrahepatic expression of IL-1β and IL-17α mRNA. To further explore potential mechanisms, we analyzed a public liver transcriptomic dataset (GSE151220) involving FMT from dysbiotic donors. Differentially expressed genes were enriched in lipid metabolism and extracellular matrix-related pathways, processes known to be involved in MAFLD progression. Conclusion: These results suggest that FMT is associated with modulation of the gut-liver axis and partial alleviation of HFCS-induced MAFLD features in mice. FMT may serve as a potential adjunctive strategy for managing MAFLD.