Internalization of Helicobacter pylori into gastric epithelial cells: mechanisms and intervention strategies

The internalization H. pylori into gastric epithelial cells may play a critical role in pathogenicity and evasion of antibacterial agents. However, many issues remain elusive. This review aimed to summarize the researches on H. pylori internalization and its associated intervention strategies.

This descriptive review systematically analyzed studies in this field.

BabA and SabA mediate H. pylori internalization, correlating with invasion into normal and inflammatory/neoplastic tissues, respectively. H. pylori invades gastric epithelial cells via zipper-like (spiral strains) and trigger (coccoid strains) pathways, rather than the single zipper-like mechanism conventionally recognized. Post-internalization, H. pylori reside in autophagosomes containing large and small vacuoles, distinct from the intracellular localization of Listeria monocytogenes and Salmonella spp. It proliferates within 12-24 h independent of virulence factors and is subsequently cleared. VacA⁺ strains exhibit lower intracellular clearance rates and a linear decline compared with VacA⁻ strains. Multiple toxins and molecular targets cooperatively mediate autophagy suppression via multipathway regulation. Probiotics, natural medicines, polymeric compounds and sonodynamic therapy represent promising interventions with translational potential. Critical knowledge gaps remain regarding the direct association between H. pylori internalization and eradication failure, invasion into non-gastric cancer cells, and the undefined intracellular survival time window of wild-type strains.

Unlike other bacteria, H. pylori invades gastric epithelial cells via two pathways and evades intracellular immunity through specific toxins. However, knowledge gaps persist. Future research should focus on these gaps and promote the translational application of potential interventions.