Beyond Antibiotics: Alternative Strategies Targeting Helicobacter pylori Resistance

Abstract The escalating global prevalence of antibiotic-resistant Helicobacter pylori strains has undermined conventional eradication therapies, heightening the burden of associated conditions such as gastritis, peptic ulcers and gastric malignancies. Emerging non-antibiotic alternatives, including natural and synthetic compounds, probiotics and vaccine candidates, offer potential solutions to combat these infections effectively. Natural and synthetic compounds provide promising anti- H. pylori effects, primarily through bacterial membrane disruption, urease inhibition, virulence gene suppression and biofilm prevention. in vitro and in vivo studies support the robust activity of natural agents, while synthetic counterparts demonstrate potent bactericidal and anti-adherence capabilities, though rigorous clinical validation is still required. Probiotic strains enhance eradication rates when combined with antibiotics, reduce treatment-related adverse effects, modulate gut microbiota and attenuate gastric inflammation and carcinogenesis. Vaccine development encompasses whole-cell, subunit and DNA platforms targeting key virulence factors, showing immunogenicity and protective efficacy in preclinical models, yet is limited by variable clinical translation and insufficient large-scale trials. Despite promising advancements, challenges persist, including inconsistent efficacy and a need for more rigorous human studies. Future efforts should emphasize combinatorial therapies, refined delivery systems, and thorough safety evaluations to integrate these strategies into clinical practice, fostering sustainable management of H. pylori in a post-antibiotic era.