A critical review on In Vivo and Ex Vivo models for the investigation of Helicobacter pylori infection

Abstract

Helicobacter pylori is a stomach-dwelling bacterium with a crude global prevalence of nearly 45% in adults and 35% in children and adolescents. Chronic H. pylori infection and the resulting inflammation are major causes of gastritis, peptic ulcer disease and gastric cancer. Since its discovery in 1982, various animal models have been proposed to recreate the specific pathophysiological interactions between H. pylori and the human host. These infection models have been instrumental in dissecting the key drivers of H. pylori colonization, persistence and mediators of host immune responses. However, a comprehensive understanding of the molecular triggers for malignant transformation of the gastric mucosa is still lacking. Vaccine development in this area has stalled, as promising candidates identified through animal studies have failed in advanced human clinical trials. Currently, H. pylori eradication is heavily reliant on different antimicrobial agents. As with other bacterial pathogens, the growing antimicrobial resistance in H. pylori remains a major challenge, making eradication therapy increasingly complex and prolonged, over time. Recent drug approvals have mostly been for newer combinations of conventional antibiotics and proton pump inhibitors. Thus, the development of novel treatments and innovative models are crucial for advancing the drug development pipeline. This review encompasses the development and recent advances in animal and non-animal models of H. pylori gastric infection and its applications in investigating novel therapeutics and vaccine candidates.

Keywords: Helicobacter pylori; animal models; antimicrobial resistance; gastric cancer; gastric organoids; gastritis; peptic ulcer disease.

Figure 1

Pathogenesis of H. pylori infection within the gastric epithelium. Three main stages of H. pylori pathogenesis can be studied: i) bacterial attachment to and colonization of the stomach mucosa; ii) the host’s immune response and H. pylori’s immune-evasive mechanisms; and iii) the pathological consequences of chronic infection (Elbehiry et al., 2023) Created with BioRender.

Figure 2

Various in vivo models for the study of H. pylori pathogenesis. This figure illustrates various animal models employed in the study of H. pylori infection and its pathogenesis. Early infection models, including pigs, cats, and dogs, were initially used before the development of mouse-adapted H. pylori strains. Mice remain the most commonly used model, available in wildtype, knockout, and transgenic varieties. Mongolian gerbils are effective in emulating H. pylori-induced gastritis, while guinea pigs, with stomach structures and gastritis features similar to humans, allow for consistent, long-term bacterial colonization studies. Non-human primates, such as rhesus macaques, are useful for advanced studies on H. pylori vaccines and therapeutics, despite limitations due to cost and ethical considerations. Wax moth larvae (Galleria mellonella) present a cost-effective infection model, suitable for investigating bacterial pathogenicity and testing new antimicrobials. Created with BioRender.

Figure 3

Organoid-based models of H. pylori infection. Gastric organoids can be derived from mouse or human tissue explants, adult somatic cells or stem cells. Created with BioRender.