Antibiotic intervention reshapes gut microbiome and modulates deoxynivalenol-induced gut - liver axis disturbances.

Deoxynivalenol (DON) is a prevalent foodborne mycotoxin, and its toxicity is closely associated with gut-liver axis dysfunction. However, the role of antibiotic-induced gut microbiome modulation in DON-induced intestinal and hepatic injury remains unclear. In this study, mice were exposed to DON with or without antibiotic (ABX) treatment for 4 weeks to investigate the contribution of gut microbiome to DON toxicity. DON exposure significantly impaired growth performance and induced hepatic injury, as evidenced by increased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and endotoxin (LPS) levels, accompanied by systemic inflammatory responses. Mechanistically, DON disrupted gut microbiome homeostasis, reduced microbial diversity, and compromised intestinal barrier integrity, leading to enhanced translocation of bacterial endotoxins into circulation. Importantly, ABX treatment was associated with reduced DON-induced hepatic injury, despite further impairment of intestinal epithelial integrity. This effect was associated with gut microbiome remodeling, decreased abundance of pro-inflammatory and LPS-associated bacterial taxa, and altered LPS-TLR4/MyD88-related inflammatory signaling responses in the liver. Moreover, correlation analysis revealed weakened associations between specific microbial genera and hepatic inflammatory markers in the ABX-treated group, suggesting a decoupling of microbiome-liver inflammatory crosstalk. Collectively, these findings suggest that DON-induced hepatotoxicity involves intestinal barrier impairment and gut microbiome-associated endotoxin signaling. ABX reshapes gut microbial communities and modulates LPS-related hepatic inflammatory responses, highlighting the potential role of the gut-liver axis in mycotoxin-associated toxicity.