Role of the gastric ecosystem in Helicobacter associated gastritis

The second leading cause of cancer death, gastric cancer, is associated with infection by Helicobacter pylori but the mechanism for the disease is still unknown. Since infection with H. pylori does not always result in gastric adenocarcinoma in the mouse; we infect with H. felis which results in gastric adenocarcinoma within twelve to fifteen months of infection. We hypothesize that Helicobacter-associated gastric adenocarcinoma is secondary to alterations induced in the protective mucus lining by the immune response to Helicobacter. Chemokines play a role in the movement and localization of inflammatory cells in disease. CXCL15, a member of the ELR+ CXC chemokine family known for neutrophil recruitment, was only expressed strongly in lung. Due to the common mucosal system of the stomach and the lung, CXCL15 expression was analyzed in the murine gastrointestinal tract. Strong expression is now reported in the gastrointestinal, urogenital, and endocrine system. Due to neutrophil infiltrates in H. felis infection, expression of CXCL15 was analyzed in our gastritis model and was highly increased after eight weeks. Alterations are seen in the mucin and trefoil factor family in the human model, but no comprehensive study has been done in the mouse model of H. felis infection. Analysis of the mucin changes showed that muc5ac was lost in the mouse model, which mimics the human disease. An increase in the expression of muc4 and muc5b is evident in the disease, indicating a loss of muc5ac with a gain of muc4 and muc5b correlating with disease progression. The stomach, which was originally thought to be a sterile environment, has been shown to contain numerous pathogens. The role of other microbial components, besides Helicobacter, has not been studied in this disease model. Through analysis of H. felis infection in a gnotobiotic (B6.GB) model and a defined flora model (B6.ASF), it was shown that the B6.GB and B6.ASF animals had similar histology but did not clear the bacteria. This along with an altered expression in Th17 and Tregs has led to the knowledge that there are several mechanisms for the gastric histology.