Active Helicobacter pylori infection causes chronic gastritis and disrupts gastric mucosal function.

Active Helicobacter pylori (H. pylori) is a highly adapted gastric pathogen that establishes lifelong colonization in the human stomach. If left untreated, the infection invariably initiates a profound inflammatory response that severely compromises the gastric lining.

Clinical and pathophysiological evidence

• Initiation of chronic gastritis: H. pylori utilizes survival factors, particularly urease, to hydrolyze urea and neutralize local stomach acid, enabling stable colonization of the gastric epithelium. This persistence triggers robust activation of inflammatory pathways—including NF-κB, NLRP3, and TNF-α—recruiting lymphocytes, macrophages, and neutrophils to the lamina propria, which directly drives chronic gastritis.
• Gastric acid dysregulation: The anatomical distribution of H. pylori-induced inflammation dictates gastric secretory function. Antral-predominant inflammation impairs somatostatin release, causing hypergastrinemia and hyperchlorhydria. Conversely, corpus-predominant gastritis leads to parietal cell atrophy and the downregulation of the H⁺/K⁺-ATPase proton pump, resulting in hypochlorhydria or achlorhydria.

Mucosal barrier mechanisms

• Tight-junction disruption: H. pylori compromises the mucosal barrier through both CagA-dependent and CagA/VacA-independent mechanisms. The virulence factor CagA translocates into host cells, directly associating with and relocalizing key apical junctional complex proteins like ZO-1 and JAM, while inhibiting PAR1/MARK kinases to disrupt cell polarity.
• Increased paracellular permeability: Independently of CagA, H. pylori urease induces myosin light chain phosphorylation, causing occludin internalization. This is further exacerbated by IL-1RI–ROCK pathway activation, which remodels the claudin network. Together, these processes increase paracellular permeability, allowing back-diffusion of luminal acid and antigens.

Bottom line

• Active H. pylori infection causes chronic gastritis that systematically disrupts normal gastric mucosal function by dismantling epithelial tight junctions, increasing paracellular permeability, and altering acid-secretory homeostasis based on the pattern of mucosal inflammation.