College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095 Jiangsu Province, China.
Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing 210095 Jiangsu Province, China.
J Agric Food Chem. 2023 Mar 8;71(9):4144-4152. doi: 10.1021/acs.jafc.3c00252. Epub 2023 Feb 27.
The etiology of inflammatory bowel diseases (IBDs) involves complex genetic and environmental factors such as mycotoxin contamination. Deoxynivalenol (DON), a well-known mycotoxin, contaminates food and feed and can induce intestinal injury and inflammatory response. The dose of DON in many foods is also below the limit, although the dose of DON exceeds the limit. The present study aims to evaluate the effects of the nontoxic dose of DON on colitis induced by dextran sodium sulfate (DSS) and the mechanism in mice. The results showed a nontoxic dose of DON at 50 μg/kg bw per day exacerbated DSS-induced colitis in mice as demonstrated by increased disease activity index, decreased colon length, increased morphological damage, decreased occludin and mucoprotein 2 expression, increased IL-1β and TNF-α expression, and decreased IL-10 expression. DON at 50 μg/kg bw per day enhanced JAK2/STAT3 phosphorylation induced by DSS. Adding JAK2 inhibitor AG490 attenuated the aggravating effects of DON on DSS-induced colitis by reversing the morphological damage, occludin and mucoprotein 2 expression increased, IL-1β and TNF-α expression increased, and IL-10 expression decreased. Taken together, a nontoxic dose of DON could aggravate DSS-induced colitis via the JAK2/STAT3 signaling pathway. This suggests that DON, below the standard limit dose, is also a risk for IBD and may be harmful to the health of humans and animals, which could provide the basis for establishing limits for DON.
炎症性肠病（IBD）的病因涉及复杂的遗传和环境因素，如霉菌毒素污染。脱氧雪腐镰刀菌烯醇（DON）是一种众所周知的霉菌毒素，污染食物和饲料，可诱导肠道损伤和炎症反应。许多食物中的 DON 剂量虽低于限量，但 DON 剂量超过限量的情况也时有发生。本研究旨在评估非毒性剂量 DON 对葡聚糖硫酸钠（DSS）诱导的结肠炎的影响及其在小鼠中的作用机制。结果表明，50μg/kg bw·d 的非毒性 DON 加重了 DSS 诱导的结肠炎，表现为疾病活动指数增加、结肠长度缩短、形态损伤加重、occludin 和粘蛋白 2 表达降低、IL-1β 和 TNF-α 表达增加、IL-10 表达降低。DON 增强了 DSS 诱导的 JAK2/STAT3 磷酸化。添加 JAK2 抑制剂 AG490 可通过逆转形态损伤、增加 occludin 和粘蛋白 2 的表达、降低 IL-1β 和 TNF-α 的表达、增加 IL-10 的表达，从而逆转 DON 对 DSS 诱导的结肠炎的加重作用。综上所述，非毒性剂量的 DON 可通过 JAK2/STAT3 信号通路加重 DSS 诱导的结肠炎。这表明 DON 在限量标准以下也是 IBD 的一个风险因素，可能对人类和动物的健康有害，这为 DON 限量的制定提供了依据。
