Natural small-molecule compounds targeting Helicobacter pylori virulence factors: A promising strategy for overcoming antibiotic resistance

Helicobacter pylori (H. pylori) infection is an important causal factor of gastritis, peptic ulcer, and gastric cancer. High infection rates and the increasing challenge of antibiotic resistance worldwide have prompted an urgent need to develop novel therapeutic options and antimicrobial agents. This review focuses on the potential of natural small-molecule compounds as novel anti-H. pylori agents-a promising approach that mitigates the risk of resistance development and maintains the microbiome's ecological balance. We detail how H. pylori virulence factors, including urease, CagA, VacA, and biofilm, contribute to pathogenicity and underline the reassuring fact that naturally derived compounds sourced from plants and microorganisms have shown remarkable efficacy in inhibiting these virulence factors. Some compounds also exhibit synergistic effects with conventional antibiotics, potentially overcoming challenges associated with resistant strains. Furthermore, we discuss recent advancements in identifying novel drug targets within the H. pylori virulence spectrum, offering insights into future directions for research and development in H. pylori therapy.