Host age at experimental Helicobacter pylori infection shapes epithelial development of mouse gastric organoids

Abstract

The bacterium Helicobacter pylori colonises gastric glands, which triggers direct responses to bacterial activity and genetic modifications of the host. While most frequently asymptomatic, infection can cause stomach cancer through a stepwise sequence from chronic gastritis to carcinoma, involving induction of stem cell-like properties of epithelial cells. We tested the effect of host age at infection on epithelial development in a mouse organoid model, where mice were infected as neonates or adults, for one month. To isolate the effects of host genetic modification, gastric organoids were grown in the absence of H. pylori and sequenced and imaged. We found that H. pylori infection early in life resulted in a larger size of the derived organoids. The expression of marker genes in organoids for different cell types was dependent on host age, suggesting a decrease in pit cells and an increase in endocrine cells with age. H. pylori infection early in life accelerated this age dependent shift, and we propose that the cell type profile affects the host response to infection.