Helicobacter pylori, a Group I carcinogen, infects over half the global population and is a leading cause of gastric cancer. Standard triple therapy with proton pump inhibitors (PPIs) and antibiotics frequently fails, often due to antibiotic resistance and host-specific factors. Emerging evidence highlights the critical role of host genetics in treatment outcomes. Polymorphisms in drug-metabolizing enzymes like CYP2C19 affect PPI efficacy, necessitating personalized dosing. Genetic variations in drug transporters (e.g. P-gp) and immune-related genes (e.g. cytokines, TLRs) further influence antibiotic pharmacokinetics, inflammatory responses, and bacterial persistence. Additionally, the interaction between H. pylori and gastric mucins, governed by expression and glycosylation patterns, affects bacterial adherence and disease severity. This review synthesizes how host-genetic variations in drug metabolism, immunity, and mucin biology interact with bacterial virulence to dictate infection persistence and treatment success. A deeper understanding of these host-pathogen mechanisms is vital for developing tailored eradication strategies. Integrating genetic profiling into clinical practice promises to overcome treatment failure, curb antibiotic resistance, and advance precision medicine for H. pylori-associated diseases. For this review, PubMed was searched for articles published primarily between January 2018 and October 2025 using the keywords. Earlier seminal studies were also included when relevant.
Khazali et al. (2026) studied this question.