Curdlan alleviates non-alcoholic fatty liver disease by enriching butyrate-producing gut microbiota-liver axis.

The gut microbiota-liver axis is a critical target for non-alcoholic fatty liver disease (NAFLD) intervention, yet effective strategies to restore gut microbiota balance and mitigate hepatic metabolic inflammation remain limited. Curdlan, a Food and Drug Administration-approved microbial exopolysaccharide, is widely used as a food additive, but its role in modulating the gut-liver axis to combat NAFLD has never been explored. Here, we demonstrate that curdlan alleviates high-fat and fiber-deficient (HFFD) diet-induced NAFLD by orchestrating gut microbiota remodeling and enhancing gut-liver crosstalk associated with the enrichment of butyrate-producing bacteria. In the mouse model of NAFLD, curdlan significantly attenuated hepatic steatosis, inflammation, and M1 macrophage infiltration. Hepatic transcriptome analysis revealed that curdlan modulated immune response and metabolism pathways, as further evidenced by the improvement of the NFκB-PTP1B-Akt signaling axis. Crucially, curdlan reversed gut barrier disruption by enhancing tight junction proteins and enriching butyrate-producing genera (Clostridium_sensu_stricto_1, Anaerovorax, Roseburia, Turicibacter, and others), thereby increasing serum butyrate levels. Integrative correlation analysis revealed a significant correlation between butyrate-producing bacteria, increased serum butyrate levels, reduced serum lipopolysaccharide, and downregulated hepatic proinflammatory cytokines. Strikingly, Clostridium butyricum supplementation recapitulated the protective effects of curdlan, suggesting a role for butyrate in mediating gut-liver interactions. These findings establish curdlan as a novel prebiotic and metabolic modulator with therapeutic potential for NAFLD and support the translational application of functional food additives in metabolic disease management.