Helicobacter pylori and Inflammatory Bowel Disease: Unraveling the Complex Interactions and Clinical Implications

ABSTRACT Helicobacter pylori infection has been extensively studied in relation to various gastrointestinal disorders, with emerging evidence suggesting a significant association with inflammatory bowel disease (IBD). Epidemiological studies consistently demonstrate an inverse relationship between H. pylori infection and IBD development, particularly Crohn's disease (CD). Meta‐analyses reveal a significantly lower prevalence of H. pylori among IBD patients compared to healthy controls, supporting the hypothesis of a potential protective effect. This negative correlation appears particularly strong for virulent strains expressing CagA, suggesting strain‐specific immunomodulatory properties. The protective mechanisms may involve H. pylori's ability to modulate host immune responses and maintain gut microbial homeostasis. Experimental models show that H. pylori colonization can induce regulatory T‐cell responses and downregulate pro‐inflammatory cytokines, potentially creating an immunological balance that protects against IBD development. Conversely, H. pylori eradication has been associated with increased IBD incidence and disease flares, possibly through disruption of established microbial ecosystems and immune regulation. Clinical observations further support this relationship, demonstrating that H. pylori‐positive CD patients often experience milder disease courses with fewer complications. However, the interaction remains complex, as H. pylori infection may also exert detrimental effects in certain contexts. The bacterium's influence appears to depend on multiple factors, including infection timing, strain characteristics, and host genetic background. Current evidence highlights the crucial interplay between H. pylori, gut microbiota composition, and mucosal immunity in shaping IBD pathogenesis. Future research should focus on elucidating precise molecular mechanisms and evaluating whether targeted modulation of H. pylori could offer therapeutic potential, while considering potential risks.