Helicobacter pylori phages: resource landscape, translational challenges, and engineered antibacterial strategies

Helicobacter pylori (H. pylori) is a globally prevalent gastric pathogen whose increasing antimicrobial resistance has reduced the efficacy of conventional eradication regimens. Bacteriophages and phage-derived products have therefore attracted growing interest as alternative antimicrobial strategies against H. pylori. However, progress in this field remains constrained by the limited availability of cultivated phages, the underexplored reservoir of prophages and uncultivated phages, narrow host range, and poor stability under gastric conditions. In this review, we summarize the current landscape of H. pylori phage research, including both virulent and temperate phages, and discuss how genome-based mining is expanding access to previously inaccessible phage resources. We further examine recent application-oriented advances, including artificial intelligence-assisted endolysin discovery, receptor-binding protein engineering for host-range expansion, and targeted delivery platforms designed to improve phage stability and site-specific activity in the stomach. Finally, we highlight key translational barriers, including biosafety evaluation, functional validation, and in vivo efficacy. Together, these advances provide a framework for evaluating phage-based and phage-derived antimicrobial strategies for H. pylori control, while highlighting the need for rigorous functional validation, biosafety assessment, and in vivo efficacy testing.