# Epithelial Hypusination Regulates Helicobacter pylori-induced Gastric Inflammation

## TL;DR

This study shows that a specific chemical modification in stomach cells, called hypusination, helps drive inflammation caused by Helicobacter pylori infection, suggesting new treatment strategies.

## Contribution

The study reveals that epithelial hypusination promotes H. pylori-induced inflammation without affecting bacterial levels, offering a novel therapeutic target.

## Key findings

- Epithelial hypusination is increased in H. pylori-infected gastric tissue.
- Mice lacking hypusination in epithelial cells show reduced inflammation after H. pylori infection.
- Hypusination affects inflammatory protein expression and immune response pathways in infected cells.

## Abstract

Hypusine is a unique amino acid synthesized on the eukaryotic initiation factor 5A (EIF5A) from the polyamine spermidine by deoxyhypusine synthase (DHPS). Hypusination of EIF5A plays a key role in translation. Here, we examined the contribution of the epithelial hypusination pathway to gastric inflammation induced by Helicobacter pylori. Immunohistochemical analyses revealed increased expression of DHPS and hypusinated EIF5A (EIF5AHyp) in the gastric mucosa of patients with H. pylori gastritis compared to uninfected individuals, notably within gastric epithelial cells (GECs) and immune infiltrates. Then, we created a mouse model with epithelial-specific deletion of Dhps (DhpsΔepi) and confirmed the reduction of DHPS and EIF5AHyp in GECs. H. pylori-infected DhpsΔepi mice exhibited an attenuation of gastric histologic inflammation scores compared with infected Dhpsfl/+ controls, without alteration in bacterial colonization levels. Quantitative proteomics of isolated GECs showed that Dhps deletion altered the expression of proteins involved in organismal injury, cancer, and gastrointestinal diseases in naïve mice. Upon H. pylori infection, inflammatory and immune response proteins, including signaling factors and immunoglobulin mediators, were less induced in DhpsΔepi GECs, and pathways linked to tissue injury and inflammation were selectively downregulated. Together, these findings demonstrate that epithelial hypusination supports H. pylori-driven gastric inflammation without affecting bacterial persistence. Targeting DHPS-dependent EIF5A hypusination may thus represent a novel therapeutic strategy to limit H. pylori-associated mucosal injury and disease progression.