Heat-stable enterotoxin induced apoptosis in small intestine epithelial cells via mitochondrial oxidative phosphorylation pathway.

Newborn piglet diarrhea caused by enterotoxigenic Escherichia coli (ETEC) causes serious economic losses in the swine industry worldwide. Heat-stable enterotoxins (STa) secreted by ETEC can damage the intestine, resulting in villus atrophy and shedding, which is the main cause of diarrhea in newborn piglets; however, the mechanism is not clear. This experiment was conducted in vivo (three-day-old suckling mice) and in vitro (IPEC-J2 cells) to explore the effect of STa on the intestinal epithelium by comparing the differences after infection with STa toxin-secreting E. coli O142 or STa-knockout E. coli O142ΔestA. The results showed that STa caused diarrhea, small intestinal edema, atrophy and rupture of small intestinal villi, and death in a dose-dependent manner in mice, and downregulated oxidative phosphorylation (OXPHOS) in IPEC-J2 cells. Activation of the mitochondria-mediated cell apoptosis pathway through excessive reactive oxygen species (ROS) production induces injury of the small intestinal villi, leading to diarrhea in piglets.