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Accessible homeostatic gastric organoids reveal secondary cell type-specific host-pathogen interactions in Helicobacter pylori infections

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Bibliographic Details
Title: Accessible homeostatic gastric organoids reveal secondary cell type-specific host-pathogen interactions in Helicobacter pylori infections
Authors: Moritz Hofer, Youlim Kim, Nicolas Broguiere, François Gorostidi, Jessica A. Klein, Manuel R. Amieva, Matthias P. Lutolf
Source: Nat Commun
Nature Communications, Vol 16, Iss 1, Pp 1-9 (2025)
Nature communications, vol. 16, no. 1, pp. 2767
Publisher Information: Springer Science and Business Media LLC, 2025.
Publication Year: 2025
Subject Terms: Helicobacter pylori, Science, Stomach, Epithelial Cells, Article, Organoids/microbiology, Organoids/cytology, Organoids/pathology, Helicobacter pylori/physiology, Humans, Helicobacter Infections/microbiology, Helicobacter Infections/pathology, Helicobacter Infections/immunology, Gastric Mucosa/microbiology, Gastric Mucosa/cytology, Gastric Mucosa/pathology, Gastric Mucosa/immunology, Host-Pathogen Interactions, Homeostasis, Epithelial Cells/microbiology, Lab-On-A-Chip Devices, Stomach/microbiology, Helicobacter Infections, Organoids, Gastric Mucosa
Description: Despite the high prevalence of gastric diseases like gastric cancer and peptic ulcer disease attributed to Helicobacter pylori infections, there is still only a limited understanding of the underlying mechanisms. Existing in vitro models are either two-dimensional systems lacking the structural complexity of the gastric architecture, or complex three-dimensional systems that pose challenges for experimental access. In this study, we introduce a patterned homeostatic human gastric organoid-on-a-chip system with bilateral access that is capable of modeling H. pylori niche establishment and persistent colonization of the gastric epithelium. We show that in physiological apical acidic conditions, our organ-on-a-chip can generate pit cells of higher maturity in contrast to traditionally grown organoids. Upon infection with H. pylori for up to 6 days, these mature pit cells exhibit a distinctive response from other cell types, which was previously uncharacterized. Beyond its application in studying H. pylori infection, the increased structural and functional relevance of our model offers broader significance as a versatile platform for advancing our understanding of gastric epithelial cell interactions, gastric mucosal immunity, and host-pathogen interactions.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 2041-1723
DOI: 10.1038/s41467-025-57131-y
Access URL: https://pubmed.ncbi.nlm.nih.gov/40113752
https://doaj.org/article/ccdcfc5161874d3fb1fbdcbc7bc667dd
https://serval.unil.ch/resource/serval:BIB_8C26BDEDC1CE.P001/REF.pdf
https://serval.unil.ch/notice/serval:BIB_8C26BDEDC1CE
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_8C26BDEDC1CE6
Rights: CC BY NC ND
Accession Number: edsair.doi.dedup.....1c9a7e901ab6c7e6de80fe24ab25be46
Database: OpenAIRE
Description
Abstract:Despite the high prevalence of gastric diseases like gastric cancer and peptic ulcer disease attributed to Helicobacter pylori infections, there is still only a limited understanding of the underlying mechanisms. Existing in vitro models are either two-dimensional systems lacking the structural complexity of the gastric architecture, or complex three-dimensional systems that pose challenges for experimental access. In this study, we introduce a patterned homeostatic human gastric organoid-on-a-chip system with bilateral access that is capable of modeling H. pylori niche establishment and persistent colonization of the gastric epithelium. We show that in physiological apical acidic conditions, our organ-on-a-chip can generate pit cells of higher maturity in contrast to traditionally grown organoids. Upon infection with H. pylori for up to 6 days, these mature pit cells exhibit a distinctive response from other cell types, which was previously uncharacterized. Beyond its application in studying H. pylori infection, the increased structural and functional relevance of our model offers broader significance as a versatile platform for advancing our understanding of gastric epithelial cell interactions, gastric mucosal immunity, and host-pathogen interactions.
ISSN:20411723
DOI:10.1038/s41467-025-57131-y