Gastric organoids: Advancing the study of H. pylori pathogenesis and inflammation

For decades, traditional in vitro and in vivo models used for the study of Helicobacter pylori infection have relied heavily on the use of gastric cancer cell lines and rodents. Major challenges faced by these methods have been the inability to study cancer initiation in already cancerous cell lines, and the difficulty in translating results obtained in animal models due to genetic differences. These challenges have prevented a thorough understanding of the pathogenesis of disease and slowed the development of cancer therapies and a suitable vaccine against the pathogen. In recent years, the development of gastric organoids has provided great advantages over the traditional in vivo and in vitro models due to their similarities to the human stomach in vivo, their ease of use, and the capacity for long‐term culture. This review discusses the advantages and limitations of existing in vivo and in vitro models of H. pylori infection, and how gastric organoids have been applied to study H. pylori pathogenesis, with a focus on how the pathogen interacts with the gastric epithelium, inflammatory processes, epithelial repair, and cancer initiation. The potential applications of organoids to address more complex questions on the role of hormones, vaccine‐induced immunity are also discussed. Significance Statement Organoid cultures offer advantages over conventional in vitro models and are providing new opportunities for modeling H. pylori disease. This review discusses how gastric organoids have enabled progress in understanding the mechanisms of H. pylori pathogenesis. We focus on recent work on initial interactions with the gastric epithelium, inflammatory processes, epithelial repair, and gastric carcinogenesis. In the next 5 years, the use of gene‐edited organoids and more complex organoid models using co‐culture with immune and other cell populations provide exciting potential for studying inflammation, cancer initiation, and even vaccine‐induced protection against H. pylori.