Helicobacter pylori infection in a mouse model: Development, optimization and inhibitory effects of antioxidants

Abstract: Helicobacter pylori is a human pathogen strongly associated with chronic type B gastritis, peptic ulcer disease, gastric cancer and MALT lymphoma. Our aims were to establish a mouse model of H. pylori infection, to study pathogenesis of gastritis and gastric cancer and to investigate new treatment strategies in this model. Both spiral and coccoid forms of H. pylori strains 17874, 25 and 553/93 caused chronic gastritis in BALB/cA mice during 30 weeks of infection. Infection with strain 553/93 displayed the most severe gastritis. Specific antibodies were detected using ELISA and immunoblot in mice infected with H. pylori following 4 weeks for 17874 spirals, and 16 weeks for 17874 coccoids, and both sprials and coccoids of two other strains. Dietary factors influenced the abilities to recover H. pylori from the infected mice through culture. One diet, without fish meal and heated at 140-150oC, gave the optimal H. pylori colonization and highest inflammation score in murine stomach among 4 commercial rodent diets tested. The changes were most dramatic (100% to 10-20% infection rate) when the infection was carried out in animals already fed on a specific diet. A H. pylori strain 119/95 (CagA and VacA positive) was found to predominate (90.5%) in the murine stomach from inocula containing nine H. pylori strains by RAPD-PCR among 577 colonies recovered from mice. C57BL/6 and BALB/cA mice showed higher inflammation scores than CBA/Ca or NMRI mice at 4 and/or 10 weeks post-inoculation. Subsequently C57BL/6 mice (n=5) inoculated with a H. pylori mouse passaged strain 119/95 developed a gastric squamous cell papilloma after 13 months. Three out of five animals developed high-grade B-cell lymphoma derived from a MALT lymphoma at the squamous-corpus border with manifestations also in the liver, spleen and kidney. An astaxanthin-rich algal meal from the microalga Hamatococcus pluvialis and vitamin C inhibit H. pylori growth at 0.3125 to 2.5 mg/ml (astaxanthin content, 6.25 to 50 mg/ml) and 0.5 to 2 mg/ml in vitro respectively. Furthermore, these antioxidants decreased the gastric colonization and inflammation significantly in infected BALB/cA mice. The effect on inhibition of H. pylori infection by the astaxanthin-rich algal meal was found to occur simultaneously with a modulation H. pylori-induced T-lymphocyte response, switching from a Th1- to a Th1/Th2-response. These studies illustrate that H. pylori can induce chronic gastritis and gastric lymphoma in an optimized mouse model. Dietary factors influence H. pylori infection and antioxidants may become a new treatment strategy against H. pylori infection in humans.