Abstract：
Mycotoxin contamination has become a major food safety issue and greatly threatens human and animal health. Patulin (PAT), a common mycotoxin in the environment, is exposed through the food chain and damages the gastrointestinal tract. However, its mechanism of enterotoxicity at the genetic and metabolic levels remains to be elucidated. Herein, the intestinal histopathological and biochemical indices, transcriptome, and metabolome of C57BL/6 J mice exposed to different doses of PAT were successively assessed, as well as the toxicokinetics of PAT in vivo. The results showed that acute PAT exposure induced damaged villi and crypts, reduced mucus secretion, decreased SOD and GSH-Px activities, and enhanced MPO activity in the small intestine and mild damage in the colon. At the transcriptional level, the genes affected by PAT were dose-dependently altered in the small intestine and fluctuated in the colon. PAT primarily affected inflammation-related signaling pathways and oxidative phosphorylation in the small intestine and immune responses in the colon. At the metabolic level, amino acids decreased, and extensive lipids accumulated in the small intestine and colon. Seven metabolic pathways were jointly affected by PAT in two intestinal sites. Moreover, changes in PAT products and GST activity were detected in the small intestinal tissue but not in the colonic tissue, explaining the different damage degrees of the two sites. Finally, the integrated results collectively explained the toxicological mechanism of PAT, which damaged the small intestine directly and the colon indirectly. These results paint a clear panorama of intestinal changes after PAT exposure and provide valuable information on the exposure risk and toxic mechanism of PAT.
摘要：
霉菌毒素污染已成为一个重大的食品安全问题，极大地威胁着人类和动物的健康。Patulin(PAT),环境中常见的霉菌毒素，通过食物链暴露并损害胃肠道。然而,其在遗传和代谢水平上的肠毒性机制仍有待阐明。在这里，肠道组织病理学和生化指标，转录组，对C57BL/6J小鼠暴露于不同剂量PAT的代谢组进行了连续评估，以及PAT在体内的毒物动力学。结果表明，急性PAT暴露会导致绒毛和隐窝受损，粘液分泌减少，降低SOD和GSH-Px活性，并增强小肠中的MPO活性和结肠中的轻度损伤。在转录水平，受PAT影响的基因在小肠中呈剂量依赖性改变,在结肠中呈波动.PAT主要影响小肠中的炎症相关信号通路和氧化磷酸化以及结肠中的免疫应答。在代谢水平，氨基酸减少，以及大量脂质在小肠和结肠中积累。在两个肠道部位PAT共同影响了七个代谢途径。此外，在小肠组织但在结肠组织中未检测到PAT产物和GST活性的变化，解释两个站点的不同损坏程度。最后,综合结果共同解释了PAT的毒理学机制，直接损害小肠和间接损害结肠。这些结果描绘了PAT暴露后肠道变化的清晰全景图，并提供了有关PAT暴露风险和毒性机制的有价值信息。
