Dysbiosis and NKG2D system activation in corpus-dominant lymphocytic gastritis. Pathogenesis of corpus-dominant lymphocytic gastritis

Corpus-dominant lymphocytic gastritis (LyG) is characterized by a CD8+ T-cell infiltration of the stomach epithelium due to a so far uncharacterized mechanism. While Helicobacter pylori is typically undetectable in LyG, patients respond to H. pylori antibiotic eradication therapy, suggesting a non-H. pylori microbial trigger for the disease. Comparative microbiota analysis of specimens from LyG, H. pylori gastritis and healthy controls precluded involvement of H. pylori in LyG but identified Propionibacterium acnesas a possible disease trigger. In addition, the natural killer group 2 member D (NKG2D) system and the proinflammatory cytokine IL15 are significantly upregulated in the gastic mucosa of LyG patients, and gastric epithelial cells respond to microbe-derived stimuli, including live P. acnes and the microbial products short-chain fatty acids, with the induction of NKG2D ligands. Together, our findings identify P. acnes as a possible causative agent for LyG, which is dependent on the NKG2D system and IL15 activation.