An Exploratory Study on Cyclocodon lancifolius Fruit Pre-Treatment Against Acute Alcohol-Induced Liver Injury: Associations with Gut Microbiota and SCFAs

Cyclocodon lancifolius fruit (CF), a functional food widely consumed in Southwest China, exhibits potent antioxidant activity and considerable commercial importance. However, its protective effects against acute alcohol-induced liver injury (ALI) and the underlying mechanisms remain to be fully elucidated. This exploratory study examined the hepatoprotective effect of CF pre-treatment in an acute binge ethanol-induced mouse model. CF pre-treatment significantly attenuated hepatic pathology, as evidenced by reduced serum ALT/AST levels and mitigated mitochondrial damage. It also ameliorated oxidative stress with Keap1 downregulation and Nrf2 upregulation. Furthermore, 16S rRNA sequencing revealed that CF pre-treatment was associated with increased abundance of Prevotella and enhanced acetate production. Fecal microbiota transplantation (FMT) suggested that the transfer of CF-modulated fecal material could partially reproduce the hepatoprotective phenotype, although the specific role of live microbes versus soluble metabolites requires further verification. In conclusion, CF pre-treatment alleviates acute alcohol-induced liver injury, which is accompanied by alterations in the gut microbiota, SCFAs, and the hepatic Keap1/Nrf2 pathway.