Helicobacter pylori-induced gastritis in guinea pigs: Model development, diagnostic methods and comparison with mouse protocols

Detta är en avhandling från Department of Laboratory Medicine, Lund University

Sammanfattning: Helicobacter pylori is a gram-negative spiral-shaped bacterium that colonizes the human stomach and causes gastric inflammation, gastric and duodenal peptic ulcers, gastric cancer and MALT-lymphoma. A novel guinea pig model of H. pylori infection was developed. Infection was induced by oral inoculation and was confirmed by cultivation from the stomach mucosa. The infection led to severe gastric inflammatory changes and a detectable serum antibody response similar to that in humans. When infected by H. pylori, guinea pigs were found to develop more severe gastritis than mice. The infection induced an acute-phase response in guinea pigs, as revealed by the elevated serum C3 levels obtained, and appeared to cause elevated serum cholesterol levels, suggesting a possible link between H. pylori infection and cardiovascular disease. The effects on H. pylori-infected guinea pigs of dietary supplements consisting of a combination of antioxidant vitamins and selenium were evaluated. Animals receiving these supplements displayed a lesser density of H. pylori colonization in the stomach than control animals and their gastric inflammation appeared to be suppressed. It was concluded that in order to obtain optimal gastric inflammation in the guinea pig model the antioxidant levels in the feed should be kept low. H. pylori infection in guinea pigs was followed for a five-month period. It was found to persist and to be accompanied by severe gastric inflammation. Control animals tested for Helicobacter by use of culture methods and a genus-specific PCR protocol were found to be free of natural Helicobacter infection. Methods of monitoring H. pylori colonisation were evaluated in both mice and guinea pigs. Of two commercial H. pylori faeces-antigen tests assessed in mice, a test based on monoclonal antibodies displayed 100% accuracy, whereas a polyclonally based test sometimes gave false positive results, probably by cross-reacting with a natural murine Helicobacter infection. Indigenous Helicobacter ganmani infection in the mouse colony was detected by PCR-denaturing gradient gel electrophoresis. The polyclonal antibody test was found to cross-react in vitro with several non-pylori Helicobacter species, including species reported in humans. Analyses of faecal samples from guinea pigs, in contrast to mice, by the use of an antigen test or PCR methods were found unable to detect the H. pylori infection. In conclusion, the investigation considers the development and optimisation of experimental H. pylori infection in guinea pigs, and also explores different methods of monitoring the infection. The study shows the guinea pig to be a viable model for studying H. pylori-related gastric and possible extra-gastric manifestations.

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