Modification of gastric mucin oligosaccharide expression in rhesus macaques after infection with Helicobacter pylori

Gastroenterology. 2009 Sep;137(3):1061-71, 1071.e1-8. doi: 10.1053/j.gastro.2009.04.014. Epub 2009 Apr 16.

Abstract

Background & aims: Helicobacter pylori attaches to mucin oligosaccharides that are expressed on host gastric epithelium. We used the rhesus macaque model to characterize the effect of H. pylori infection on gastric mucin oligosaccharides during acute and chronic infection.

Methods: Specific pathogen (H. pylori)-free rhesus macaques were inoculated with H. pylori J166. Biopsy specimens of the gastric antrum were obtained 2 and 4 weeks before and 2, 8, and 24 weeks after infection with H. pylori. O-linked mucin oligosaccharides were released from gastric biopsy samples by beta-elimination and profiled by matrix-assisted laser desorption/ionization mass spectrometry. Similar studies were performed on gastric biopsy samples from H. pylori-infected and uninfected humans. Formalin-fixed, paraffin-embedded sections of rhesus antrum biopsy samples were stained with H&E, periodic acid-Schiff stain, and antibody to MUC5AC, the predominant mucin expressed in the stomach.

Results: H. pylori-induced gastritis was accompanied by an acute and dramatic decrease in diversity and relative abundance of O-linked mucin oligosaccharides in the rhesus stomach, which largely recovered during the 24-week observation period. These variations in oligosaccharide abundance detected by mass spectrometry were reflected by changes in periodic acid-Schiff-positive material and expression of MUC5AC over time. Relatively few differences were seen in gastric mucin oligosaccharide composition between H. pylori-infected and uninfected patients, which is consistent with the results in rhesus macaques because infection occurs in childhood.

Conclusions: Acute H. pylori infection is accompanied by a dramatic but transient loss in mucin oligosaccharides that may promote colonization and persistence.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Gastric Mucins / metabolism*
  • Gastritis / metabolism
  • Gastritis / microbiology
  • Gastritis / pathology
  • Helicobacter Infections / metabolism*
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori* / isolation & purification
  • Macaca mulatta
  • Male
  • Mucin 5AC / metabolism
  • Oligosaccharides / metabolism*
  • Pyloric Antrum / microbiology
  • Pyloric Antrum / pathology
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Gastric Mucins
  • Mucin 5AC
  • Oligosaccharides