Florfenicol-induced gut microbiome dysbiosis triggers chronic disease pathways and intestinal damage in the benthic fish (Leiocassis longirostris)

The sub-therapeutic use of antibiotic use in aquaculture disrupts host-microbiota balance and poses ecological risks, though its chronic effects on benthic species remain poorly understood. Here we demonstrate that exposing Chinese longsnout catfish (L. longirostris) to florfenicol at a standard aquaculture dose of 10 mg/kg per day for five days induced severe intestinal dysbiosis and functional impairment. We observed a significant 43.65 % reduction in microbial gene abundance and a 96.16 % decrease in host mRNA expression, accompanied by a marked 69.11 % increase in host DNA contamination, indicating the collapse of the mucosal barrier and loss of microbial ecological function. The core microbiota shifted from beneficial Cetobacterium, which produces antioxidant and neuroprotective metabolites, to opportunistic genera such as Clostridium and Acinetobacter. Metabolically, florfenicol exposure resulted in a significant 29.3 % suppression of functional pathways and a pronounced 5.8-fold upregulation of electron transport genes including petB and fprB, which is associated with the activation of chronic diseases pathways such as Parkinson’s, Huntington’s and Diabetic cardiomyopathy. These pathways all share common mechanisms with mitochondrial dysfunction and ROS metabolism and further trigger chronic pathological changes including intestinal mucosal injury, mitochondrial oxidative stress and cell apoptosis. Additionally, the loss of Cetobacterium impaired the synthesis of key metabolites such as ascorbic acid and lovastatin acid, exacerbating intestinal structural damage and apoptosis. The transfer risk of antibiotic resistance genes was also significantly elevated. These findings reveal persistent microbiome dysfunction and heightened chronic disease risks following conventional antibiotic exposure, underscoring the urgency of reevaluating antibiotic usage in sustainable aquaculture.