Enterobacter sakazakii enhances epithelial cell injury by inducing apoptosis in a rat model of necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is an inflammatory intestinal disorder that affects 2%-5% of all premature infants. Enterobacter sakazakii, a common contaminant of milk-based powdered infant formula, has been implicated as a causative agent of sepsis, meningitis, and NEC in newborn infants, with high mortality rates. However, the role played by E. sakazakii in the pathogenesis of NEC is, to date, not known. Here, we demonstrate for the first time that E. sakazakii can induce clinical and histological NEC in newborn rats. E. sakazakii was found to bind to enterocytes in rat pups at the tips of villi and to intestinal epithelial cells (IEC-6) in culture, with no significant invasion. Exposure to E. sakazakii induced apoptosis and increased the production of interleukin-6 in IEC-6 cells and in the animal model. These data suggest that E. sakazakii could be a potential pathogen that induces NEC and triggers intestinal disease by modulating enterocyte intracellular signaling pathways.