Aim: 

The gastric mucosal barrier is classically conceived to act as a physical barrier between gastric lumen and subepithelial layers of the mucosa. However, Helicobacter pylori (H. pylori), a bacterium colonizing the luminal side of the gastric epithelium, invariably arises an immune-inflammatory response on the stromal site of the mucosa. In this study we investigated whether and how H. pylori and/or its virulence factors are able to cross the human gastric mucosal barrier directly entering epithelial cells, intercellular spaces and underlying stroma.

Methods: 

In endoscopic biopsies from H. pylori-colonized patients, we combined systematically transmission electron microscopy with immunocytochemical tests using antibodies directed against H. pylori and its main virulence factors, VacA or CagA.

Results: 

We found that in vivoH. pylori and its main virulence factors penetrate gastric epithelium, both intracellularly and through the paracellular route, up to directly contact and enter immune-inflammatory cells of underlying lamina propria as well as small blood vessels.

Conclusions: 

Our work provides in vivo evidence that H. pylori is able to directly cross the human gastric mucosal barrier so as to reach the subepithelial layers of the mucosa. Present findings, while allowing to better understand how H. pylori elicits a heavy immune-inflammatory response, demonstrate the ineffectiveness of the gastric mucosal barrier in preventing mucosal damage by a frequently occuring gastro-offensive condition such as H. pylori infection, which may lead to peptic ulcer and gastric cancer.