Tween 80 Exposure Induces Colitis by Disrupting Intestinal Tryptophan Metabolism

Inflammatory bowel disease (IBD) is a widespread public health problem worldwide, and environmental pollutants are regarded as the cause of IBD. Tween 80 (P80) may trigger IBD; however, its underlying mechanism of action has not been fully clarified, especially with respect to diet-induced susceptibility. This study systematically investigated the effect of P80 on the IBD development in male mice on a normal diet and high-fat diet (HFD) at an acceptable daily intake level. After 6 weeks of oral exposure to P80 (0.1, 1, 6%), the high-dose group of mice exhibited a significant increase in the disease activity index, a significant body weight loss, and a severe inflammatory response, with HFD markedly augmenting these effects. Multiomics results indicated that P80 exposure disrupted intestinal tryptophan metabolism and significantly reduced indole-3-acetic acid (IAA) levels. In vivo intestinal inflammation was transcriptionally regulated by genes related to the AhR/NF-κB/NLRP3 signaling pathway. Supplementing with IAA can improve inflammatory effects. In vitro studies confirmed that P80 exposure inhibited Lactobacillus from producing IAA, leading to an increase in the level of intestinal inflammation. This study revealed the specific toxic mechanism of P80-induced IBD and found that dietary factors have a synergistic toxic effect, providing new insights into the health risk assessment of environmental pollutants.