Decreased Gastric Bacterial Killing and Up-Regulation of Protective Genes in Small Intestine in Gastrin-Deficient Mouse

Dig Dis Sci. 2003 May;48(5):976-85. doi: 10.1023/a:1023068116934.

Abstract

Gastrin regulates gastric acid secretion, believed to be primarily responsible for killing ingested microbes. We examined gastric killing of gavaged E. coli in gastrin-deficient mice, which have decreased gastric acid production. Additionally, the expression of intestinal genes involved in epithelial protection were analyzed: the mucus layer glycoprotein muclin, the polymeric Ig receptor, trefoil factor 3, and small proline-rich protein 2a (sprr2a). Gastric pH was 2.5 pH units greater in gastrin-deficient mice, and E. coli survival was increased greater than 20-fold at 10 min after gavage compared to control. Muclin and sprr2a gene expression were significantly increased (2.0- and 2.6-fold) in the intestine, and antibiotic treatment reversed these effects. In conclusion, reduced gastric acid secretion results in increased survival of ingested microorganisms in gastrin-deficient mice. Bacterial survival is associated with increased expression of muclin and sprr2a in the intestine, indicating that these genes play protective roles in the intestine.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cornified Envelope Proline-Rich Proteins
  • DNA, Bacterial / analysis
  • Disease Models, Animal
  • Escherichia coli / pathogenicity*
  • Female
  • Gastric Acid / metabolism*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology
  • Gastrins / deficiency*
  • Growth Substances / genetics*
  • Hydrogen-Ion Concentration
  • Intestine, Small / metabolism
  • Intestine, Small / microbiology*
  • Intestine, Small / pathology*
  • Male
  • Membrane Proteins / isolation & purification
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mucins / metabolism
  • Muscle Proteins*
  • Neuropeptides*
  • Peptides / genetics*
  • Polymerase Chain Reaction / methods
  • Protein Precursors / isolation & purification
  • RNA, Messenger / analysis
  • Sensitivity and Specificity
  • Trefoil Factor-2
  • Trefoil Factor-3
  • Up-Regulation

Substances

  • Cornified Envelope Proline-Rich Proteins
  • DNA, Bacterial
  • Gastrins
  • Growth Substances
  • Membrane Proteins
  • Mucins
  • Muscle Proteins
  • Neuropeptides
  • Peptides
  • Protein Precursors
  • RNA, Messenger
  • Sprr2a1 protein, mouse
  • TFF3 protein, rat
  • Trefoil Factor-2
  • Trefoil Factor-3