Bongkrekic acid reprograms hepatic lipid metabolism to promote systemic organ injury.

Bongkrekic acid (BK), a highly lethal mitochondrial toxin produced by Burkholderia gladioli pathovar cocovenenans, poses a significant threat to food safety. Although clinical reports have documented its harmful effects, the underlying metabolic mechanisms driving BK toxicity remain fullly understood. In this study, we utilized multi-omics techniques to explore the impact of BK on metabolic processes across multiple organs using a mouse model. Our results demonstrated that BK treatment significantly altered the liver's cellular composition, with hepatocytes becoming the dominant cell type. Notably, distinct subpopulations of hepatocytes emerged exclusively in the BK-treated group, showing enrichment in lipid metabolism-related pathways. Trajectory analysis revealed a shift toward terminal hepatocyte states, and cell-cell communication analysis revealed enhanced interactions between BK-specific hepatocytes and immune cells, particularly those involved in cholesterol metabolism signaling. Serum metabolomics indicated significant accumulation of lipids and lipid-like molecules, reflecting systemic metabolic dysregulation. Histopathological analysis confirmed multi-organ injury, including hepatic microvesicular steatosis, renal tubular damage, neuronal injury, myocardial alterations, and pulmonary inflammation. This study advances our understanding of BK toxicity by demonstrating that BK induces widespread lipid metabolic dysregulation and multi-organ pathological damage, with the liver acting as a central metabolic hub. Moreover, our findings provide critical insights into potential therapeutic strategies, focusing on stabilizing hepatic lipid and cholesterol handling and modulating immunometabolic signaling pathways.