Modeling Lipopolysaccharide‐Elicited Inflammation Using 3D Mouse Gastric Organoids

Colonization of Helicobacter pylori (H. pylori) in stomach often causes gastritis, an inflammation of the stomach lining that is closely associated with serious conditions like ulcers and gastric cancer. Of the toxicity mechanisms, microbial lipopolysaccharide (LPS) binding to TLR4 receptor on the glandular cells activates the NF-κB pathway, inducing pro-inflammatory cytokine release and immune cell infiltration, which results in the tissue damage. However, whether LPS has any direct damaging effect on gastric epithelial cells has been in debate. By using mouse gastric organoids that were grown from the isolated glands and maintained the cellular compositions, we demonstrate various effects of variable LPS concentrations on the glandular epithelial cells, including mild promotion of cell proliferation at the low concentration and induced loss of cell polarity and altered gene expressions at the high concentration. These findings provide insights into how LPS directly affects the stomach lining.