Disruption of the biorhythm in gastric epithelial cell triggers inflammation in Helicobacter pylori-associated gastritis by aberrantly regulating NFIL3 via CagA activated ERK-SP1 pathway.

Helicobacter pylori (H. pylori) associated gastritis, marked by chronic gastric inflammation, heightens gastric cancer risk by fostering a malignancy-prone microenvironment. Disruption of the biorhythm contribute to the onset of various gastrointestinal disorders, such as gastric dyspepsia, gastric ulcers, and cancer. We aimed to investigate the functional roles and regulatory mechanisms of key biorhythm molecules in H. pylori associated gastritis. We investigated biorhythm gene expression in H. pylori-infected human gastric tissues and found significant impact on NFIL3 expression. Animal studies confirmed that H. pylori controls NFIL3 biorhythm. Clinical samples indicated a correlation between NFIL3 and gastritis severity, suggesting a regulatory role. Then, we found that H. pylori disrupt NFIL3 expression rhythm in gastric epithelial cells (GECs) through the CagA-activated ERK-SP1 pathway. Additionally, cytokines IL1β and TNFα enhance this disruption. RNA-seq and Gene set enrichment analysis (GSEA) indicated that NFIL3 positively regulates the inflammatory response during H. pylori infection. Our research highlights the crucial role of the biorhythm molecule NFIL3 in H. pylori associated gastritis. Modulating biorhythm molecules could be a promising therapeutic approach to manage disease progression, given their impact on gastrointestinal pathology.