脱氧雄酮醇（DON）是谷物和饲料中常见的毒素，接触DON会触发严重的小肠损伤和炎症，危害人类和牲畜的健康。DON处理导致Paneth细胞减少，然而Paneth细胞在DON诱导的肠道损伤中的作用尚不明确。我们利用二唑磺（40mg/kg）将小鼠的Paneth细胞数量维持在较低水平。结果显示，二唑磺介导的Paneth细胞长期破坏加剧了DON（2mg/kg）处理小鼠的肠道损伤、肠干细胞（ISC）丧失和菌群紊乱。令人意外的是，二唑磺和DON处理的小鼠中腺细胞和增殖细胞的数量增加。在二唑磺和DON处理后，Firmicutes/Bacteroidetes（F/B）比例降低，并观察到Dubosiella的丰度增加和Lactobacillus的丰度减少。溶菌酶（200U/天）补充对Paneth细胞功能的恢复改善了DON挑战后小鼠的肠道损伤和ISC丧失。此外，溶菌酶还促进了肠道器官样体的生长和ISC活性。综上所述，这些结果表明Paneth细胞在DON诱导的肠道损伤中具有保护作用。我们的研究为DON接触的治疗提供了一个新的靶点——Paneth细胞。版权所有 © 2023作者, Elsevier公司出版，保留所有权利。

Deoxynivalenol (DON) is a common toxin in grains and feeds, and DON exposure triggers severe small intestinal injury and inflammation, which harms the health of humans and livestock. DON treatment leads to a decrease in Paneth cells, whereas the role of Paneth cells in DON-induced intestinal injury is poorly understood. We utilized dithizone (40 mg/kg) to keep murine Paneth cell number at a low level. The results showed that dithizone-mediated long-term disruption of Paneth cells aggravated intestinal injury, intestinal stem cell (ISC) loss, and microbiota disorder in DON (2 mg/kg)-treated mice. Unexpectedly, the number of goblet cells and proliferative cells was boosted in mice treated with dithizone and DON. After dithizone and DON treatments, the Firmicutes/Bacteroidetes (F/B) ratio was reduced, and the increased abundance of Dubosiella and the decreased abundance of Lactobacillus were observed in mice. The functional recovery of Paneth cells by lysozyme (200 U/day) supplementation improved intestinal injury and ISC loss in mice after DON challenge. In addition, lysozyme also promoted the growth and ISC activity of intestinal organoids. Taken together, these results demonstrate the protective role of Paneth cells in DON-induced intestinal injury. Our study raises a novel target, Paneth cell, for the treatment of DON exposure.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.