Abstract
ABSTRACTGastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems.
Highlights
Helicobacter pylori is a bacterium that grows in close association with the lining of the stomach and is associated with various human gastric diseases; it causes significant morbidity and mortality worldwide
Helicobacter-induced gastric pathology in humans Chronic infection with H. pylori is strongly associated with gastric pathology, including chronic active gastritis, peptic ulcer disease, gastric adenocarcinoma and gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma)
Associated with gastritis in dogs and cats Associated with gastritis in dogs and cats In cats, hypothesized to be associated with gastric lymphoma (Bridgeford et al, 2008) Associated with gastritis Associated with gastritis No known pathology Gastritis, gastric pre-malignant lesions and gastric adenocarcinoma (Fox et al, 1997) and gastric MALT lymphoma (Erdman et al, 1997) Gastric adenocarcinoma with gastritis and intestinal metaplasia Associated with gastric ulcers and erosions in tigers (Cattoli et al, 2000) Associated with gastric and oesophageal ulceration in whales and dolphins Peptic ulcer disease, gastric adenocarcinoma and gastric MALT lymphoma in humans; gastritis in dogs and cats
Summary
Helicobacter pylori is a bacterium that grows in close association with the lining of the stomach and is associated with various human gastric diseases; it causes significant morbidity and mortality worldwide. Helicobacter-induced gastric pathology in humans Chronic infection with H. pylori is strongly associated with gastric pathology, including chronic active gastritis (see Glossary, Box 1), peptic ulcer disease, gastric adenocarcinoma and gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma). Of these outcomes, the most significant in terms of mortality is gastric adenocarcinoma. Key Surface mucous cell Stem cell Mucous neck cell Parietal cell Endocrine cell Chief cell
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