迄今为止，仍不清楚溴氰菊酯（DLM）的摄入是否会对结肠组织造成损害。因此，本研究旨在阐明长期暴露于低剂量DLM对结肠组织的影响及其潜在机制。小鼠经DLM（0.2 mg/kg/天）或DLM联合N-乙酰-L-半胱氨酸（NAC）（50 mg/kg/天）处理8周。人结肠癌细胞（HCT-116）被处理DLM（0、25、50或100µM）、NAC（2mM）或过表达过氧化还蛋白1（PRDX1）靶向质粒48小时。使用DLM快速检测卡检测DLM。使用苏木精-伊红染色和透射电镜评估结肠损伤。使用免疫荧光染色（IF）、免疫印迹（WB）和流式细胞术（FC）测定细胞凋亡。使用MitoTracker、JC-1和谷胱甘肽（GSH）检测来检测线粒体氧化应激。通过16S rDNA测序，鉴定肠道菌群。长期经口给予小鼠DLM后，DLM积聚在结肠组织和粪便中。有趣的是，我们的结果显示，即使在低剂量下，长期摄入DLM会导致严重的体重减轻，并减少疾病活动指数评分和结肠长度。IF、WB和FC的结果显示，DLM诱导了结肠组织和细胞的凋亡。MitoTracker、JC-1和GSH检测显示，DLM增加了结肠上皮细胞的线粒体应激。机制研究表明，线粒体应激和凋亡的增加是由PRDX1抑制介导的。进一步实验显示，PRDX1的过表达显著减轻了DLM诱导的氧化应激损伤和凋亡。此外，我们观察到，长期暴露于DLM改变了小鼠肠道菌群的组成，包括Odoribacter和Bacteroides的增加以及Lactobacillus的减少。DLM暴露后，小鼠肠道微生物的种群丰富度减少。体内外NAC补充剂缓解了DLM诱导的氧化应激损伤、结肠上皮细胞凋亡和肠道菌群失调。长期暴露于DLM，即使在低剂量下，也会对结肠组织造成损害，这是不能忽视的。应严格控制类似DLM的农药在农业生产过程中的生产和使用。Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

To date, it is unclear whether deltamethrin (DLM) intake causes damage to colon tissue. Hence, in this study, we aimed to clarify the effect of long-term exposure to low-dose DLM on colon tissues, and its potential mechanisms.Mice were treated with DLM (0.2 mg/kg/day) or DLM combined with N-acetyl-l-cysteine (NAC) (50 mg/kg/day) for 8 weeks. Human colon cancer cells (HCT-116) were treated with DLM (0, 25, 50, or 100 µM), NAC (2 mM), or overexpression plasmids targeting peroxiredoxin 1 (PRDX1) for 48 h. DLM was detected using a DLM rapid detection card. Colon injury was evaluated using haematoxylin and eosin staining and transmission electron microscopy. Apoptosis was determined using immunofluorescence staining (IF), western blotting (WB) and flow cytometry (FC) assays. MitoTracker, JC-1, and glutathione (GSH) detection were used to detect mitochondrial oxidative stress. Intestinal flora were identified by 16 S rDNA sequencing.DLM accumulation was detected in the colon tissue and faeces of mice following long-term intragastric administration. Interestingly, our results showed that, even at a low dose, long-term intake of DLM resulted in severe weight loss and decreased the disease activity index scores and colon length. The results of IF, WB, and FC showed that DLM induced apoptosis in the colon tissue and cells. MitoTracker, JC-1, and GSH assays showed that DLM increased mitochondrial stress in colonic epithelial cells. Mechanistic studies have shown that increased mitochondrial stress and apoptosis are mediated by PRDX1 inhibition. Further experiments showed that PRDX1 overexpression significantly reduced DLM-induced oxidative stress injury and apoptosis. In addition, we observed that chronic exposure to DLM altered the composition of the intestinal flora in mice, including an increase in Odoribacter and Bacteroides and a decrease in Lactobacillus. The gut microbial richness decreased after DLM exposure in mice. Supplementation with NAC both in vivo and in vitro alleviated DLM-induced oxidative stress injury, colonic epithelial cell apoptosis, and gut microbial dysbiosis.Chronic exposure to DLM, even at small doses, can cause damage to the colon tissue, which cannot be ignored. The production and use of pesticides such as DLM should be strictly regulated during agricultural production.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.