Helicobacter pylori, a gram negative microaerophilic urease positive and motile spiral shaped bacterium is the etiologic agent of human chronic superficial (active) gastritis. In humans, H. pylori is the primary cause of gastric ulcers and atrophic gastritis and a probable risk factor for the development of gastric carcinoma and gastric mucosa associated lymphoid tissue (MALT) lymphoma, presumably because of infection induced epithelial cell proliferation and increased mucosal exposure to orally ingested carcinogens in an acid neutral environment in the former and immunogenic overstimulation in the latter. The organism exhibits remarkable genomic variation among bacterial isolates, but genomic homogeneity within infected individuals suggesting that it is not subjected to selectional pressures by the host to ecological competition with other bacterial species. Normal gastric defenses which prevent colonization by most bacteria, do not hinder H. pylori and may restrict delivery of specific antibody or immune cells to the gastric lumen. The gnotobiotic piglet, uniformly susceptible to oral infection from birth onward, is the most widely recognized infection and colonization model of human bacterial gastritis. Human origin virulent H. pylori, strain 26695, is adapted to optimal growth in piglets. This motile, urease positive isolate is CagA and cytotoxin (VacA) positive and achieves colonization levels (10(7) to 10(8) colony forming units/g mucosa) within 24 hr after oral inoculation. In addition, other bacterial strains (N6, WV99) but not all (Tx30a) colonize piglets; laboratory passed strains colonize poorly if at all. In pigs, as in humans, infection is restricted to the gastric microenvironment, persists in that location for at least 3 mo (pigs) or yr (humans) in spite of vigorous local and systemic immune responses. The microbe has a specific affinity for gastric mucus and adheres to gastric mucosal epithelia where it stimulates a multifocal or diffuse mononuclear lymphoplasmacytic inflammatory response with development of lymphoid follicles (pigs and children) and superficial neutrophilic infiltrates plus the lymphoplasmacytic lymphofollicular gastritis in adult humans. In piglets, the gastric inflammatory lesion can be modified to include the neutrophilic component by parenteral but not oral immunization with a killed autologous bacterin prior to infection. Gastric mucosal epithelial lesions, now recognized as diagnostic for H. pylori gastric infection, also occur in infected piglets. These include mucus depletion, epithelial cell vacuolation and degeneration, epithelial hyperplasia and necrosis with resultant gastric erosions and ulcerations. The piglet model permits in vivo determination of putative bacterial virulence factors such as motility and/or presence of flagella, vacuolating cytotoxin (VacA) expression, urease enzyme presence and/or activity and infectivity of coccoid forms. In addition, a variety of conventional and experimental pharmaceuticals, antimicrobials and biologicals have been subjected to preclinical evaluation and efficacy in infected piglets. Both microbe related and host associated factors effect the pathogenesis of various components of the disease process. The relative importance of each alone or in combination can be determined in gnotobiotic piglets which possess a susceptible gastric microenvironment devoid of confounding variables such as concurrent commensal microbes, their products or effects on the host, diet, varying H. pylori burdens and strain differences, age, preexistent immunity and/or concurrent antimicrobial and antacid therapies.
