Low Dose of Deoxynivalenol Aggravates Intestinal Inflammation and Barrier Dysfunction Induced by Enterotoxigenic Infection through Activating Macroautophagy/NLRP3 Inflammasomes.

The toxicity of deoxynivalenol (DON) in healthy humans and animals has been extensively studied. However, whether the natural-low-dose DON is scatheless under unhealthy conditions, especially intestinal injury, is unknown. Infection of enterotoxigenic (ETEC) is a classical intestinal injury model. In this study, we explored the effects of low-dose DON on intestinal injury induced by the ETEC infection and the underlying mechanism in piglets, mice, and IPEC-J2 monolayer cells. Results showed that significant growth slowdown, severe diarrhea, and intestinal damage, bacterial multiplication, and translocation were observed in the experimental group (low-dose DON, 0.75 mg/kg in feed for piglets, and 1 mg/kg body weight for mice, combined with the ETEC infection). Meanwhile, more aggressive intestinal inflammation and barrier dysfunction were observed in animals and IPEC-J2 monolayer cells. Higher expression levels of NLRP3 inflammasome and LC3B were observed in jejunum and IPEC-J2 in the experimental group. After treatment with NLRP3 or caspase1 inhibitors, excessive intestinal inflammation rather than barrier dysfunction in the experimental group was limited. CRISPR-Cas9-mediated knockout of LC3B alleviated intestinal inflammation and barrier dysfunction and also inhibited NLRP3 inflammasome. In conclusion, a low dose of DON aggravates intestinal inflammation and barrier dysfunction induced by the ETEC infection by activating macroautophagy and NLRP3 inflammasome.