Novel wheat peptide GYP ameliorates Helicobacter pylori infection with AMPK activation

Helicobacter pylori (H. pylori) is a common microaerobic gram-negative bacteria. It colonizes the stomach of human causing gastritis and then gastric cancer. Currently, H. pylori infection is clinically limited to antibiotic-based therapies. With the widespread use of antibiotics, resistance of H. pylori to antibiotics may be a major reason for treatment failure. Therefore, it is imperative to develop alternative strategies to eradicate H. pylori. In the present study, a peptide GYP was identified from wheat germ protein hydrolysate. The minimum bactericidal concentration of synthesized GYP on 1 × 108 CFU/mL H. pylori was 5 mg/mL, accompanied with cell membrane disruption. Meanwhile, GYP inhibited the urease activity of H. pylori and decreased toxin gene vacuolar cytotoxin A and cytotoxin-associated gene A expression. Furthermore, GYP prevented H. pylori colonization in mouse stomach, and subsequently reduced inflammatory cell infiltration, eliminated gastric vascular congestion and improved gastritis induced by H. pylori. In consistent with this, GYP interfered adhesion of H. pylori on the surface of human gastric mucosal epithelial cells. It further protected gastric mucosal epithelial cells against apoptosis triggered by H. pylori. Therefore, GYP might be a promising anti-H. pylori peptide for the alleviation of H. pylori-induced inflammation and subsequent impairment of gastric mucosa.