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

Abstract

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.

Organoid‐Based Human Stomach Micro‐Physiological System to Recapitulate the Dynamic Mucosal Defense Mechanism

“…The utilization of hAOs has effectively addressed the limitations associated with neoplastic or cancerous gastric epithelial cell lines, allowing for the integration of multiple types of gastric epithelial cells and enabling the manifestation of complex gastric functions. [ 42 ] In this study, exploiting MPS technology facilitated dynamic cell culture through co‐cultivation in a separate channel or controlled fluid flow, resulting in a more sophisticated microenvironment control for maintaining gastric epithelial homeostasis. Specifically, the maintenance of mesenchymal niche function of gMSCs through fluid flow played a crucial role in supporting the physiological transit‐amplifying process, which is essential for maintaining a balance between gastric epithelial proliferation and differentiation.…”

Modelling esophageal adenocarcinoma and Barrett’s esophagus with patient-derived organoids

“…pylori undergo cell death upon attachment to the human cells ( Segal et al, 1996 ; Kusters et al, 1997 ). Promisingly, patient-derived gastric organoid models allow for longer-term in vitro culture of H. pylori with PDOs, facilitating and accelerating research in this field ( Chakrabarti and Zavros, 2020 ; Idowu et al, 2022 ). It stands that no equivalent studies exist using EAC PDO models to interrogate host-microbiome interactions, highlighting a clear gap in EAC research and a novel application of EAC PDOs.…”

Current and Future Perspectives in the Diagnosis and Management of Helicobacter pylori Infection

“…Urea, gastric acid, lactate, and reactive oxygen species have all been identified as signals for these receptors; urea in particular is secreted by the gastric epithelium and is thought to play a significant role in bacterial colonization [ 45 ]. However, undiscovered chemicals may also be implicated in this process [ 46 ]. Hp utilizes urease to protect itself from the surrounding acid environment.…”

“…Urease breaks urea down into ammonia and other useful metabolites, increasing the pH in the microenvironment to create a thin, pH-neutral layer around the bacterial cell, allowing it to survive the gastric acid. This barrier reduces the viscosity of the mucin gel lining the stomach wall and allows the bacteria to move freely through the mucous toward the gastric glands that it will ultimately colonize [ 46 , 47 ].…”