Accessible Homeostatic Gastric Organoids Reveal Secondary Cell Type-Specific Host-Pathogen Interactions in Helicobacter Pylori Infections

Despite the high prevalence of gastric diseases like gastric cancer and peptic ulcer disease, largely attributed to Helicobacter pylori infections, an understanding of the underlying mechanisms remains limited. Current in vitro models suffer from poor physiological relevance and limitations in live, long-term observations and experimental access. In this study, we introduce a homeostatic human gastric organoid-on-a-chip system with bilateral access, capable of modelling H. pylori niche establishment and persistent colonization of the gastric epithelium.We show that in physiological apical acidic conditions, the model is able to generate mature pit cells, which are absent in traditionally grown organoids. Upon infection with H. pylori for up to 6 days, these mature pit cells exhibit a distinctive response, contrary to existing paradigms. Beyond its immediate relevance for studying H. pylori infection, this model with structurally and functionally increased relevance holds broader significance by providing a versatile platform to advance our understanding of gastric epithelial cell interactions as well as gastric mucosal immunity and host-pathogen interactions. Overall design: Human gastric epithelial cells from organoids were grown in a Transgel chip in either apically acidic, neutral or air-liquid interface and analyzed with scRNAseq. Secondly, H. pylori-infected samples were analyzed at two different timepoints.