Identification and mechanistic investigation of novel adhesion inhibitory peptides against Helicobacter pylori from corn protein hydrolysates

According to the World Gastrointestinal Organization, the infection rate of Helicobacter pylori in the global population is more than 50%. Intervening H. pylori adhesion and colonization through functional food components is an effective strategy to inhibit H. pylori infection. This study is the first to evaluate the antagonistic mechanism of corn protein hydrolysates against H. pylori from multiple paths based on the process of H. pylori infection. In this study, corn protein hydrolysates with adhesion inhibitory activity against H. pylori were prepared by Protease P (Protease P-CPH). The antagonistic potential of Protease P-CPH against H. pylori was analyzed from multi-perspective. Thereafter, potential adhesion inhibitory peptides in the Protease P-CPH were isolated and characterized. The results demonstrated that Protease P-CPH could bond to H. pylori to inhibit its adhesion to human gastric mucosal epithelial cells (GES-1 cells). Protease P-CPH also inhibited H. pylori urease activity, and kinetic analysis revealed that its inhibition of urease was a mixed-type inhibition. In addition, the Protease P-CPH intervention significantly down-regulated the mRNA expression levels of adhesin and urease-related genes (P＜0.05). These results indicated that Protease P-CPH antagonized H. pylori infection through the synergistic combination from a multi-perspective. Two novel adhesion inhibitory peptides (LPPPFY and VPWCPQ) antagonizing H. pylori were further identified. Molecular docking results showed two novel peptides could bind to adhesins mainly through hydrogen bonding and hydrophobic interactions, and their activity and binding effect have also been demonstrated in vitro. This study helps to elucidate the antagonism mechanism of H. pylori infection of corn protein hydrolysates, while highlights the potential application of its as a more economical and effective functional food. •Two novel adhesion inhibitory peptides against H. pylori are identified.•Novel peptides bind to adhesins by hydrogen bonding and hydrophobic interactions.•Corn protein hydrolysate inhibits H. pylori adhesion in multiple paths.