Helicobacter pylori is a Gram-negative bacterium that infects over 50% of the world's population. This organism causes various
gastric diseases such as chronic
gastritis,
peptic ulcer, and
gastric cancer. H. pylori possesses
lipopolysaccharide, which shares structural similarity to
Lewis blood group antigens in gastric mucosa. Such antigenic mimicry could result in immune tolerance against
antigens of this pathogen. On the other hand, H. pylori colonize gastric mucosa by utilizing adhesins, which bind Lewis
blood group antigen-related
carbohydrates expressed on gastric epithelial cells. In chronic
gastritis, lymphocytes infiltrate the lamina propria, and such infiltration is facilitated by
6-sulfo sialyl Lewis X-capped O-
glycans,
peripheral lymph node addressin (PNAd), on high endothelial venule (HEV)-like vessels. The number of HEV-like vessels increases as chronic
inflammation progresses. Furthermore, PNAd formed on HEV-like vessels disappear once H. pylori is eradicated. These results indicate that PNAd plays an important role in H. pylori-associated
inflammation. H. pylori barely colonizes gland mucous cell-derived
mucin where alpha1,4-GlcNAc-capped O-
glycans exist. In vitro experiments show that alpha1,4-GlcNAc-capped O-
glycans function as a natural
antibiotic to inhibit H. pylori growth. We recently identified
cholesterol alpha-
glucosyltransferase (CHLalphaGcT) using an expression cloning strategy and showed that this
enzyme is specifically inhibited by
mucin-type O-
glycans like those present in deeper portions of the gastric mucosa. These findings show that a battery of
carbohydrates expressed in the stomach is closely associated with pathogenesis and also prevention of H. pylori-related diseases.