The Impact of Imidacloprid in Dietary Residues on Intestinal Damage and the Increased Risk of Enterotoxigenic Escherichia coli Infection

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 <i>Escherichia coli</i> (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.