Abstract
Infection of the human stomach with Helicobacter pylori may develop into gastritis, ulceration, adenocarcinoma and mucosal lymphomas. The pathogenic mechanisms that determine the clinical outcome from this microbial-epithelial interaction remain poorly understood. An increasing number of reports suggests that disruptions of epithelial barrier function may contribute to pathology and postinfectious complications in a variety of gastrointestinal infections. The aim of this review is to critically discuss the implications of H pylori persistence on gastric disease, with emphasis on the role of myosin light chain kinase, claudins and matrix metalloproteinases in gastric permeability defects, and their contribution to the development of cancer. These mechanisms and the associated signalling events may represent novel therapeutic targets to control disease processes induced by H pylori, a microbial pathogen that colonizes the stomach of over 50% of the human population.
Highlights
A growing body of evidence in the scientific literature supports the hypothesis that H pylori may alter epithelial tight junctional components and disrupt gastric barrier function, and that these effects may be strain-dependent
This mechanism may represent a common route towards the development of postinfectious food allergies, which have been reported in association with H pylori as well as other enteric pathogens [99,100]
In pancreatic cells, claudin-4 expression inversely correlates with metastatic potential [53,54], and it was recently observed that loss of claudin-4 may be implicated in the development of gastric adenocarcinoma [55]
Summary
There is growing evidence that, in addition to being unable to clear the infection, the T helper cell (Th)-1 polarity of the host response to H pylori infection contributes to the development of disease in the host. For reasons that remain unclear, only a relatively small number of H pylori-infected patients ever proceeds from gastritis to neoplasia formation [4] Together, these observations are consistent with the hypothesis that the oncogenic potential of H pylori may be strain- and/or host-dependent, and related to specific signalling events of the epithelialmicrobial interaction. Loss of cell-to-cell adhesion is a well-established precursor of gastric adenocarcinomas, and abnormalities of the adherens junctional protein E-cadherin have been found to contribute to this phenomenon as well as to the migratory potential of tumour cells [48,49] In keeping with these findings, functional inhibition of E-cadherin through mutations initiates
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