Zahra Sadeghloo

Abstract Colorectal cancer (CRC), a major global health burden, is the second leading cause of cancer deaths. This review examines the link between Helicobacter pylori infection and CRC, highlighting its role beyond gastric pathology. Affecting over half the world’s population, H. pylori is associated with increased CRC risk through direct and indirect mechanisms. Direct pathways include toxins like CagA and VacA, which drive inflammation, and hypergastrinaemia, which promotes colorectal cell proliferation. Indirectly, H. pylori induces immune dysregulation, shifts to immune-evasive coccoid forms, survives intracellularly, releases oncogenic vesicles, disrupts autophagy, alters non-coding RNAs by dysregulating their expression profiles and contributes to gut microbiota dysbiosis. Additionally, we discuss the potential of probiotic interventions to counteract H. pylori ’s pathogenic effects by restoring gut microbial balance, reducing inflammation and modulating immunity by regulating cytokine and T-cell profiles. Future research should translate these molecular insights into clinical applications, including evaluating whether H. pylori eradication reduces CRC risk in high-risk populations and assessing the preventive potential of specific probiotic strains in controlled human trials.