Probiotic bacterial ghosts enhance oral astaxanthin delivery to alleviate non-alcoholic fatty liver

Astaxanthin (AXT) is a promising natural bioactive compound for the nutritional intervention of non-alcoholic fatty liver (NAFL), however, its poor stability and limited oral bioavailability restrict its practical application. In this study, a novel probiotic-derived oral delivery system, designated AXT@LPGs, was developed by loading AXT into Lactiplantibacillus plantarum bacterial ghosts (LPGs) to enhance its efficacy against NAFL. In vivo experiments demonstrated that LPGs significantly improved the intestinal accumulation and retention of AXT. Pharmacokinetic evaluation further revealed that the peak plasma concentration of AXT@LPGs was approximately 1.3-fold higher than that of free AXT, and the systemic exposure of AXT was increased by approximately 49%. In a high-fat diet-induced NAFL mouse model, AXT@LPGs effectively alleviated hepatic lipid accumulation and oxidative stress. Compared with the model group, AXT@LPGs reduced hepatic triglyceride, free fatty acid, and malondialdehyde levels by 71.51%, 43.8%, and 60.56%, respectively, indicating improved lipid metabolism and enhanced antioxidant capacity. Furthermore, AXT@LPGs downregulated pro-inflammatory cytokine levels, remodeled gut microbiota composition, and corrected hepatic lipid metabolic disturbances. Overall, this study demonstrates that LPGs are effective biomimetic oral carriers for improving the bioavailability and biological efficacy of AXT, providing a promising nutritional intervention strategy for the prevention and management of NAFL.