Cathelicidin- derived PR39 protects enterohemorrhagic Escherichia coli O157:H7 challenged mice by improving epithelial function and balancing the microbiota in the intestine.

The zoonotic enterohaemorrhagic Escherichia coli (EHEC) O157:H7 can disrupt intestinal epithelial barrier function and in turn leading to serious intestinal and systemic disease. PR39 could effectively inhibit the growth of Gram-negative bacteria, but there is little knowledge of its effects on intestinal barrier function and the microbiota in E. coli-challenged mice. In this study, an intestinal disease caused by EHEC O157:H7 was established, to analyze the effect of PR39 on EHEC O157:H7 induced intestinal epithelial barrier injury and disorder. Interestingly, PR39 attenuated EHEC O157:H7-induced systemic symptoms and significantly decreased mortality and the degree of E. coli shedding in faeces. Furthermore, the infiltration index of macrophages and neutrophils in intestine of the PR39 treatment group were obviously attenuated, along with the level of apoptosis. PR39 treatment group had distinctly improved tight junction associated proteins' expression after EHEC O157:H7 caused injury. Additionally, the sequencing analysis of cecum microbiota showed that PR39 altered the abnormal increase in Bacteroides caused by EHEC O157:H7 and promoted the growth of probiotics such as Lactobacillus. In conclusion, cathelicidin-derived PR39 could effectively improve EHEC O157:H7-induced epithelial barrier injury, and dysfunction of immune and microbiota homeostasis in the intestinal tract, indicating that PR39 could be an excellent potential drug for zoonotic EHEC O157:H7-related intestinal disease.

Oral Administration of Bovine Lactoferrin-Derived Lactoferricin (Lfcin) B Could Attenuate Enterohemorrhagic Escherichia coli O157:H7 Induced Intestinal Disease through Improving Intestinal Barrier Function and Microbiota.

Lactoferricin (Lfcin) B, derived from lactoferrin in whey, has attracted considerable attention because of its multiple biological functions. Zoonotic enterohemorrhagic Escherichia coli (EHEC) O157:H7 has adverse effects on intestinal epithelial barrier function, leading to serious intestinal disease. In this study, the EHEC O157:H7-induced intestinal dysfunction model was developed to investigate the effects of Lfcin B on EHEC O157:H7-induced epithelial barrier disruption and microbiota dysbiosis. Results showed that the inflammatory infiltration indexes in the jejunum of Lfcin B-treated animals were significantly decreased. Lfcin B administration also significantly improved ZO-1 and occludin expression following O157:H7-induced injury. Finally, microbiota analysis of the cecal samples revealed that Lfcin B inhibited the O157:H7-induced abnormal increase in Bacteroides. Therefore, Lfcin B efficiently attenuated O157:H7-induced epithelial barrier damage and dysregulation of inflammation status, while maintaining microbiota homeostasis in the intestine, indicating that it may be an excellent food source for prevention and therapy of EHEC O157:H7-related intestinal dysfunction.