Abstract：
Florfenicol, a widely used veterinary antibiotic, has now been frequently detected in various water environments and human urines, with high concentrations. Accordingly, the ecological risks and health hazards of florfenicol are attracting increasing attention. In recent years, antibiotic exposure has been implicated in the disruption of animal glucose metabolism. However, the specific effects of florfenicol on the glucose metabolism system and the underlying mechanisms are largely unknown. Herein, zebrafish as an animal model were exposed to environmentally relevant concentrations of florfenicol for 28 days. Using biochemical and molecular analyses, we found that exposure to florfenicol disturbed glucose homeostasis, as evidenced by the abnormal levels of blood glucose and hepatic/muscular glycogen, and the altered expression of genes involved in glycogenolysis, gluconeogenesis, glycogenesis, and glycolysis. Considering the efficient antibacterial activity of florfenicol and the crucial role of intestinal flora in host glucose metabolism, we then analyzed changes in the gut microbiome and its key metabolite short-chain fatty acids (SCFAs). Results indicated that exposure to florfenicol caused gut microbiota dysbiosis, inhibited the production of intestinal SCFAs, and ultimately affected the downstream signaling pathways of SCFA involved in glucose metabolism. Moreover, non-targeted metabolomics revealed that arachidonic acid and linoleic acid metabolic pathways may be associated with insulin sensitivity changes in florfenicol-exposed livers. Overall, this study highlighted a crucial aspect of the environmental risks of florfenicol to both non-target organisms and humans, and presented novel insights into the mechanistic elucidation of metabolic toxicity of antibiotics.
摘要：
氟苯尼考,一种广泛使用的兽用抗生素，现在已经在各种水环境和人类尿液中频繁检测到，浓度高。因此，氟苯尼考的生态风险和健康危害日益受到重视。近年来,抗生素暴露与动物葡萄糖代谢的破坏有关。然而,氟苯尼考对葡萄糖代谢系统的具体作用和潜在机制在很大程度上是未知的。在这里，斑马鱼作为动物模型暴露于环境相关浓度的氟苯尼考28天。使用生化和分子分析，我们发现接触氟苯尼考会干扰葡萄糖稳态，血糖和肝/肌糖原的异常水平证明，以及参与糖原分解的基因表达的改变，糖异生,糖原,和糖酵解。考虑到氟苯尼考的高效抗菌活性和肠道菌群在宿主糖代谢中的关键作用，然后,我们分析了肠道微生物组及其关键代谢产物短链脂肪酸(SCFA)的变化.结果表明，暴露于氟苯尼考导致肠道菌群菌群失调，抑制肠道SCFA的产生，并最终影响SCFA参与糖代谢的下游信号通路。此外，非靶向代谢组学研究显示,花生四烯酸和亚油酸代谢途径可能与氟苯尼考暴露的肝脏胰岛素敏感性变化相关.总的来说,这项研究强调了氟苯尼考对非靶标生物和人类的环境风险的一个关键方面，并提出了对抗生素代谢毒性机理阐明的新见解。
