Royal Jelly and 10‐Hydroxy‐2‐decenoic Acid Mitigate Alcoholic Fatty Liver Disease in Mice via the Gut‐Microbiota‐Metabolite Axis

Royal jelly (RJ) and its bioactive compound, 10-hydroxy-2-decenoic acid (10-HDA), have been reported to possess hepatoprotective properties, yet their mechanisms against alcoholic fatty liver disease (AFLD) remain to be fully elucidated. This study integrated 16S rRNA sequencing, untargeted metabolomics, and molecular analyses to evaluate their therapeutic potential in an AFLD mouse model. Results indicated that RJ (200 mg/kg/day) and 10-HDA (100 mg/kg/day) alleviated alcohol-induced liver injury by reducing lipid accumulation, dyslipidemia, inflammation, and oxidative stress. Furthermore, these interventions modulated gut microbiota composition by decreasing the relative abundance of Pseudomonadota and Escherichia, while increasing taxa such as Akkermansia and Lactobacillus. Metabolomic profiling suggested the involvement of key pathways, including serotonergic synapse, bile secretion, and tryptophan metabolism. In the liver, RJ and 10-HDA treatment was associated with the activation of the AMPK pathway, which promotes fatty acid β-oxidation and suppresses lipogenesis. Notably, integrated correlation analyses indicated that the restoration of certain fecal metabolites correlated with hepatic AMPK activation. Collectively, RJ and 10-HDA may mitigate AFLD by modulating the gut-microbiota-metabolite axis and the AMPK signaling pathway, supporting their potential use as dietary supplements for liver health.