College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province 210095, China.
Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing, Jiangsu Province 210095, China.
J Agric Food Chem. 2022 Mar 9;70(9):3009-3022. doi: 10.1021/acs.jafc.1c07834. Epub 2022 Feb 24.
The toxicity of deoxynivalenol (DON) in healthy humans and animals has been extensively studied. However, whether the natural-low-dose DON is scatheless under unhealthy conditions, especially intestinal injury, is unknown. Infection of enterotoxigenic (ETEC) is a classical intestinal injury model. In this study, we explored the effects of low-dose DON on intestinal injury induced by the ETEC infection and the underlying mechanism in piglets, mice, and IPEC-J2 monolayer cells. Results showed that significant growth slowdown, severe diarrhea, and intestinal damage, bacterial multiplication, and translocation were observed in the experimental group (low-dose DON, 0.75 mg/kg in feed for piglets, and 1 mg/kg body weight for mice, combined with the ETEC infection). Meanwhile, more aggressive intestinal inflammation and barrier dysfunction were observed in animals and IPEC-J2 monolayer cells. Higher expression levels of NLRP3 inflammasome and LC3B were observed in jejunum and IPEC-J2 in the experimental group. After treatment with NLRP3 or caspase1 inhibitors, excessive intestinal inflammation rather than barrier dysfunction in the experimental group was limited. CRISPR-Cas9-mediated knockout of LC3B alleviated intestinal inflammation and barrier dysfunction and also inhibited NLRP3 inflammasome. In conclusion, a low dose of DON aggravates intestinal inflammation and barrier dysfunction induced by the ETEC infection by activating macroautophagy and NLRP3 inflammasome.
脱氧雪腐镰刀菌烯醇（DON）在健康人和动物中的毒性已得到广泛研究。然而，在不健康的情况下，特别是在肠道损伤的情况下，天然低剂量 DON 是否具有危害性，目前尚不清楚。产肠毒素性大肠杆菌（ETEC）感染是一种经典的肠道损伤模型。本研究探讨了低剂量 DON 对仔猪、小鼠和 IPEC-J2 单层细胞 ETEC 感染诱导的肠道损伤的影响及其潜在机制。结果表明，实验组（饲料中低剂量 DON 为 0.75mg/kg，体重 1mg/kg，同时 ETEC 感染）出现明显的生长缓慢、严重腹泻和肠道损伤、细菌增殖和易位。同时，在动物和 IPEC-J2 单层细胞中观察到更具侵袭性的肠道炎症和屏障功能障碍。实验组中 NLRP3 炎性体和 LC3B 的表达水平更高。用 NLRP3 或半胱天冬酶 1 抑制剂处理后，实验组中过度的肠道炎症而不是屏障功能障碍受到限制。CRISPR-Cas9 介导的 LC3B 敲除减轻了肠道炎症和屏障功能障碍，并抑制了 NLRP3 炎性体。综上所述，低剂量 DON 通过激活自噬和 NLRP3 炎性体加重 ETEC 感染引起的肠道炎症和屏障功能障碍。
