Hepatoprotective Mechanisms of Lactiplantibacillus plantarum SCS7 Cell-Free Extract Against Aflatoxin B1 Toxicity

Aflatoxin B1 (AFB1) is a widespread contaminant of food and feed that poses significant risks to both human and animal health. Developing safe and effective strategies to mitigate its toxicity remains a major public health priority. In this study, we investigated the protective effects of Lactiplantibacillus plantarum SCS7 cell-free extract (CFE) against AFB1-induced liver injury using integrated in vivo (mouse) and in vitro (AML12 hepatocyte) models. CFE treatment markedly alleviated AFB1-induced hepatic damage, mitochondrial dysfunction, and gut microbiota dysbiosis. Mechanistic analyses indicate that the protective effects of CFE are associated with the alleviation of excessive mitophagy and concomitant restoration of the PINK1/Parkin signaling axis, while systemic protection is conferred through modulation of the gut-liver axis. Importantly, unlike live probiotics, CFE circumvents concern related to intestinal colonization and biosafety while maintaining multi-pathway efficacy. Notably, this study identifies a previously unrecognized role for probiotic-derived metabolites in organelle quality control, demonstrating that CFE mitigates liver injury by inhibiting pathological mitophagy. Furthermore, CFE reshaped the intestinal microbiota and promoted the production of beneficial microbial metabolites, changes that were closely associated with improved hepatic homeostasis. Collectively, these findings suggest a coordinated interplay among the gut microbiota, microbial metabolites, and restoration of the PINK1/Parkin pathway, thereby providing a theoretical foundation for the development of stable, cell-free probiotic therapeutics with potential applications in food safety and public health.