Potential Mechanisms of Lactiplantibacillus plantarum WW-Fermented Pueraria lobata in Alleviating Alcoholic Liver Injury

• The fermentation of probiotics with TCM achieves synergistic efficiency. • The antioxidant properties of FLP alleviate oxidative stress. • FLP enhances gut epithelial, mucosal, and immune barriers function. • FLP reshaped gut microbiota, raising SCFAs levels. • SCFAs upregulate Gpr43 to activate liver AMPK/mTOR, inducing autophagy. Alcoholic liver disease represents a considerable public health challenge globally. Its development is driven by multiple mechanisms, including oxidative stress, inflammatory responses, and dysbiosis of intestinal microbiota. Recent studies have indicated that functional foods may effectively mitigate alcoholic liver injury, owing to their natural active constituents and favorable safety profiles. This study aimed to evaluate the protective effects of Lactiplantibacillus plantarum WW-fermented Pueraria lobata (FLP) against alcoholic liver injury. Single-factor experiments and response surface methodology were employed to optimize the fermentation conditions of strain WW for processing Pueraria lobata , determining the optimal process parameters. Furthermore, fermentation significantly increased the flavonoid content of FLP, and its antioxidant capacity was also significantly enhanced accordingly. Molecular docking analysis further revealed that puerarin, the main active component, binds stably to the Keap1 protein. Animal studies demonstrated that FLP intervention markedly alleviates alcohol-induced liver damage, restores the liver's capacity for alcohol metabolism, diminishes lipid accumulation, and attenuates oxidative stress within the liver. Additionally, FLP upregulates the expression of ZO-1, MUC2, and LGR5 in the colon, thereby enhancing intestinal barrier function and repair capacity, which subsequently reduces serum lipopolysaccharide levels and inflammatory factors. FLP effectively modulates intestinal microbiota composition and increases beneficial bacteria abundance, leading to restored intestinal levels of SCFAs and upregulation of Gpr43 gene expression. This short-chain fatty acids (SCFAs)-GPR43 signaling consequently activates the hepatic AMPK/mTOR pathway, thereby inducing protective autophagy. This study confirms that probiotic-fermented Pueraria lobata overcomes the limitations of single interventions, offering a novel synergistic strategy for treating alcoholic liver disease.