Yuan Xinlei, Wang Zihan, Wu Fang, Cheng Le, Jin Yutong, Dong Jianguo, Zheng Chenyan, Ma Yumeng, Jin Yan, Fang Bing
State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China.
Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.
Foods. 2025 Jun 17;14(12):2119. doi: 10.3390/foods14122119.
Pesticide residues in foods can disturb the intestinal barrier and microbiota, even at a very low dose; however, studies on direct consequences on intestinal health are still lacking. Here, we evaluated the damage of imidacloprid (IMI) to the intestine and the resulting defense against enterotoxigenic (ETEC) in C57BL/6J mice. After 8-week exposure to 0.06 mg /kg bodyweight/day, IMI significantly damaged intestinal structure and intestinal integrity, characterized by an increased permeability to FITC-dextran and decreased mRNA expression of tight junction proteins, as well as more broken villi and lower proportions of goblet cells and paneth cells. These were related to the suppression of the self-renewal of intestinal stem cells (ISCs), as evidenced by significantly decreased Sox9+ ISCs and increased apoptosis. Furthermore, the impaired intestinal integrity in mice exposed to low doses of IMI directly increased the susceptibility to ETEC infection and even caused death. On the other hand, exposure to 0.6 mg IMI/kg bodyweight/day lead to significantly increased contents of IL-1β and TNFα both in the intestine and serum, and significantly decreased Th1 cell and IFN-γ contents in the lamina propria during the ETEC infection. Our study suggested that the intestinal damage induced by pesticide residues would significantly decrease the defense ability of the intestine, which suggests a novel perspective when evaluating the long-term effects of food contaminates on intestinal health at low doses without significant toxicological injuries.
食品中的农药残留即使在剂量很低的情况下也会扰乱肠道屏障和微生物群；然而，关于其对肠道健康直接影响的研究仍然缺乏。在此，我们评估了吡虫啉（IMI）对C57BL/6J小鼠肠道的损伤以及由此产生的对产肠毒素大肠杆菌（ETEC）的防御作用。在以0.06毫克/千克体重/天的剂量暴露8周后，IMI显著破坏了肠道结构和肠道完整性，其特征为对异硫氰酸荧光素标记的葡聚糖通透性增加、紧密连接蛋白的mRNA表达降低，以及更多的绒毛破损、杯状细胞和潘氏细胞比例降低。这些与肠道干细胞（ISC）自我更新的抑制有关，表现为Sox9+ ISC显著减少和细胞凋亡增加。此外，暴露于低剂量IMI的小鼠肠道完整性受损直接增加了对ETEC感染的易感性，甚至导致死亡。另一方面，以0.6毫克/千克体重/天的剂量暴露于IMI会导致在ETEC感染期间肠道和血清中的IL-1β和TNFα含量显著增加，以及固有层中Th1细胞和IFN-γ含量显著降低。我们的研究表明，农药残留引起的肠道损伤会显著降低肠道的防御能力，这为评估低剂量食品污染物对肠道健康的长期影响提供了一个新的视角，而这些影响在没有明显毒理学损伤的情况下往往被忽视。
