, Volume 48, Issue 5, pp 976-985

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

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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.