Egg white ovomucin-derived glycopeptides inhibit Helicobacter pylori adhesion by acting as receptor analogs

Helicobacter pylori (H. pylori) , a class I carcinogen, infects 50-80% of the global population. Anti-adhesive therapies are emerging as promising alternatives to antibiotics for controlling bacterial infections. In this study, ovomucin hydrolysates were shown to effectively prevent H. pylori adhesion to gastric epithelial cells (GES-1 cells). Hydrolysates produced using Protease N exhibited the strongest inhibitory effect, reaching 44.8 ± 0.6% inhibition at 10 mg/mL, with a minimum antiadhesive concentration (MAC) of 0.31 mg/mL. This anti-adhesive activity is primarily attributed to glycopeptides that function as receptor analogs, binding to H. pylori . Sixteen α-ovomucin-derived peptides with potential H. pylori -binding activity were identified. Eleven permethylated glycans were characterized, all sharing a conserved pentasaccharide core of GlcNAc 2 Man 3 , with terminal residues including mannose, galactose, N-acetylgalactosamine, N-acetylhexosamine, and N-acetylneuraminic acid (Neu5Ac). Notably, only one N-glycan, Hex 5 HexNAc 4 NeuAc 2 (m/z 2,792.8), contained terminal Neu5Ac, which plays a key role in mediating H. pylori binding via sialic acid-binding adhesin (SabA) and contributes to the inhibition of bacterial adhesion to GES-1 cells. This study provides evidence supporting the potential of ovomucin hydrolysates as functional food ingredients to prevent H. pylori infection. • Ovomucin hydrolysates showed anti-adhesive activity against Helicobacter pylori. • Anti-adhesive activity resulted from the decoy action of ovomucin glycopeptides. • N-glycan Hex 5 HexNAc 4 NeuAc 2 , containing terminal Neu5Ac, mediates H. pylori binding. • Sixteen α-ovomucin peptides were identified and may mediate H. pylori binding. • Ovomucin glycopeptides have potential to prevent H. pylori infection.