Host Wnt/beta-catenin pathway triggered by Helicobacter pylori correlates with regression of gastric intestinal metaplasia after H. pylori eradication

Helicobacter pylori eradication can reverse gastric intestinal metaplasia (IM) in some but not all patients. H. pylori induces high levels of nuclear beta-catenin staining in IM tissues, as well as overexpression of cyclooxygenase-2 (COX-2). This study investigated whether the Wnt/beta-catenin pathway plays a role in IM regression following H. pylori eradication. Sixty-five H. pylori-infected patients with IM who had achieved successful H. pylori eradication provided paired gastric samples before and after eradication to analyse the persistence of IM, and to assess COX-2 and nuclear beta-catenin expression. The host genotypes of single nucleotide polymorphisms (SNPs) of the COX-2, beta-catenin (CTNNB1) and adenomatous polyposis coli (APC) genes were analysed. In addition, expression of beta-catenin, E-cadherin and phosphorylated and unphosphorylated glycogen synthase kinase 3 beta (GSK-3 beta) in cell lines challenged with H. pylori isolates from patients with and without IM persistence was compared by immunoanalysis. After a mean 33.9-month follow-up after H. pylori eradication, 44 patients (67.7 %) with IM persistence had a higher rate of high-level nuclear beta-catenin expression in IM tissue than those without IM persistence (P=0.008). The patients with IM persistence had a higher rate of AA, GG and AA APC SNP genotypes at positions 4479, 5268 and 5465, respectively, than the patients without IM persistence (P=0.022). The H. pylori isolates from the patients with IM regression after H. pylori eradication induced more phospho-GSK-3 beta in AGS cells than isolates from patients with IM persistence (P=0.011). It is likely that interactions with H. pylori and the patient's Wnt/beta-catenin genetic predisposition determine the outcome of IM persistence following H. pylori eradication.