Corn silk ameliorates fatty liver disease by modulating the gut microbiota and metabolites in the serum and liver

Corn silk, the stigma of the female flower of maize (Zea mays L.), is a medicinal and food-based homologous natural product. Previous studies have highlighted the lipid-modulating and hepatoprotective properties of corn silk; however, its effects on fatty liver disease remain unclear. C57BL/6J mice were fed an HFD and orally administered CSE. Hepatic histopathology, systemic inflammatory markers, and metabolic profiles were assessed. Gut microbiota and metabolomic analyses were integrated to identify the key regulatory axis. CSE administration significantly improved hepatic steatosis, reduced circulating lipid levels, and suppressed systemic and hepatic inflammation. Microbiota analysis revealed that CSE restructured the intestinal ecology by fostering a “competing guild” dominated by Akkermansia, which was negatively correlated with several pathobionts. Metabolomic profiling indicated that CSE significantly modulated pentose-glucuronate interconversion and primary bile acid biosynthesis. Notably, the enrichment of taurine and activation of the bile acid-FXR signaling axis were identified as pivotal mechanisms for enhancing fatty acid β-oxidation and restoring redox balance via the glutathione pathway. Our findings demonstrate that CSE effectively ameliorates FLD by modulating the gut microbiota-metabolite-liver axis. These results position CSE as a promising prebiotic and functional food candidate for the prevention and treatment of metabolic liver diseases.