Intestine in Gastrin-De_cient Mouse.pdfVIP

P1: GXB PP692-ddas-465873 DDAS.cls March 31, 2003 11:17 Digestive Diseases and Sciences, Vol. 48, No. 5 (May 2003), pp. 976–985 ( C? 2003) Decreased Gastric Bacterial Killing and Up-Regulation of Protective Genes in Small Intestine in Gastrin-Deficient Mouse FRANCIS J. SUN, DVM,* SIMRAN KAUR, PhD,? DONNA ZIEMER, BS,? SNIGDHA BANERJEE, PhD,? LINDA C. SAMUELSON, PhD,? and ROBERT C. DE LISLE, PhD? 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 ep- ithelial 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. KEY WORDS: gastrin; intestine; muclin; polymeric Ig receptor; small proline-rich protein 2a; trefoil factor3. There is strong evidence regarding the importance of gas- tric acid in controlling the microbial load that reaches the small intestine (1). In turn, gastrin is a major regulator of gastric acid secretion in the stomach, acting both directly on parietal cells and, perhaps more importantly, through enterochromaffin-like cells (2). The regulation of gastrin synthesis and release is complex and includes antral dis- tension, sto