Ovomucin Hydrolysates Reduce Bacterial Adhesion and Inflammation in Enterotoxigenic Escherichia coli (ETEC) K88-Challenged Intestinal Epithelial Cells

• Published in: Journal of agricultural and food chemistry Vol. 72; no. 13; pp. 7219 - 7229
• Main Authors: Bao, Xiaoyu, Gänzle, Michael G., Wu, Jianping
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 03.04.2024
• Subjects: adhesion; Animals; Bacterial Adhesion; Bioactive Constituents, Metabolites, and Functions; Caco-2 Cells; calcium; calcium-calmodulin-dependent protein kinase; chickens; diarrhea; Diarrhea - microbiology; egg albumen; Enterotoxigenic Escherichia coli; enterotoxins; epithelial cells; Epithelial Cells - metabolism; epithelium; Escherichia coli Infections - drug therapy; Escherichia coli Infections - microbiology; food chemistry; glycoproteins; glycosylation; Humans; inflammation; Inflammation - drug therapy; Inflammation - metabolism; Intestinal Mucosa - metabolism; intestines; mitogen-activated protein kinase; NF-kappa B - genetics; NF-kappa B - metabolism; Ovomucin; oxidative stress; pancreatin; pathogens; pepsin; Swine; ovomucin hydrolysate; intestinal epithelial cells; intestinal integrity; inflammation; Enterotoxigenic Escherichia coli K88; heat-stable toxin; tight junction
• ISSN: 0021-8561; 1520-5118; 1520-5118
• DOI: 10.1021/acs.jafc.4c00185

Enterotoxigenic Escherichia coli (ETEC) K88 is the most common cause of diarrhea in neonatal and postweaning pigs. After adhering to small intestinal epithelial cells via glycoprotein receptor recognition, the pathogen can produce enterotoxins, impair intestinal integrity, trigger watery diarrhea, and induce inflammation via nuclear factor κB (NF-κB) and mitogen-activated protein kinase phosphatase (MAPK) pathways. Inhibiting ETEC K88 adhesion to cell surfaces by interfering with the receptor-fimbriae recognition provides a promising strategy to prevent the initiation and progression of infection. Ovomucin is a highly glycosylated protein in chicken egg white with diverse bioactivities. Ovomucin hydrolysates prepared by the enzymes Protex 26L (OP) and pepsin/pancreatin (OPP) were previously revealed to prevent adhesion of ETEC K88 to IPEC-J2 cells. Herein, we investigated the protective effects of ovomucin hydrolysates on ETEC K88-induced barrier integrity damage and inflammation in IPEC-J2 and Caco-2 cells. Both hydrolysates inhibited ETEC K88 adhesion to cells and protected epithelial cell integrity by restoring transepithelial electronic resistance (TEER) values. Removing sialic acids in the hydrolysates reduced their antiadhesive capacities. Ovomucin hydrolysates suppressed ETEC-induced activation of NF-κB and MAPK signaling pathways in both cell lines. The ability of ETEC K88 in activating calcium/calmodulin-dependent protein kinase 2 (CaMK II), elevating intracellular Ca2+ concentration, and inducing oxidative stress was attenuated by both hydrolysates. In conclusion, this study demonstrated the potential of ovomucin hydrolysates to prevent ETEC K88 adhesion and alleviate inflammation and oxidative stress in intestinal epithelial cells.