Gastric and enteric Helicobacter species in animal models and in the human colon
Abstract: The Gram-negative genus of Helicobacter consists of many bacterial species that colonize a wide range of animal hosts. The genus can be divided into gastric species that colonize the stomach, and enteric species that preferentially colonize the colon and biliary tree of various animal hosts. Helicobacter pylori cause gastritis, gastro-duodenal ulcer disease and gastric adenocarcinoma and lymphoma in infected individuals. Enteric Helicobacter species cause typhlocolitis, hepatitis and neoplasia of the colon and liver in various rodent models of disease. A novel guinea pig model of H. pylori infection was developed and the infection was found to cause severe inflammatory changes in the stomach and an H. pylori-specific antibody response in infected animals after 3 and 7 weeks of infection. Different strains of H. pylori, with regards to the cagA gene and VacA protein expression, could infect mice. The infection was found to cause an H. pylori specific antibody response in mice infected with strains expressing the VacA protein. Simultaneous co-infection of mice with seven different strains of H. pylori showed evidence of colonization with two different strains. Gastritis was not apparent in mice infected with H. pylori for up to 17 weeks. H. pylori infection was found to lead to substantially more gastritis and serologic antibody response in guinea pigs than in mice. In guinea pigs, the infection was found to cause an elevation of acute-phase protein C3 and cholesterol, which could constitute a possibility to study an H. pylori trigger of extra-alimentary diseases. Helicobacter ganmani was isolated from interleukin-10 deficient mice with typhlocolitis and hepatitis. Analysis of serum antibodies demonstrated an immune response against H. ganmani in animals with disease. This recently described species of Helicobacter was implicated as the possible source of the disease found among the animals but this link needs to be evaluated in a controlled, experimental set-up. The importance of using Helicobacter-free animals for a wide range of experiments, especially when using immune deficient animals, needs to be stressed. Human colon biopsies from 20 patients with inflammatory bowel disease and other ailments were investigated for Helicobacter colonization. DNA resembling H. pylori was detected in two, Helicobacter cholecystus in one and Helicobacter muridarum in one patient. The latter two species have previously not been described in human tissue. No apparent link was found between the detection of Helicobacter species and human inflammatory bowel disease. In summary, this thesis deals with development and optimization of two animal models for H. pylori infection and also explores the role of enteric Helicobacter species in human and animal disease.
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