Abstract
BACKGROUND: Helicobacter pylori (H. pylori) may be present in the intestinal mucosa of patients with inflammatory bowel disease (IBD), which is a chronic inflammation of the gastrointestinal tract. The role of H. pylori in the pathogenesis of IBD remains unclear. In this study, bioinformatics techniques were used to investigate the correlation and co-pathogenic pathways between H. pylori and IBD. METHODS: The following matrix data were downloaded from the GEO database: H. pylori-associated gastritis, GSE233973 and GSE27411; and IBD, GSE3365 and GSE179285. Differential gene analysis was performed via the limma software package in the R environment. A protein-protein interaction (PPI) network of DEGs was constructed via the STRING database. Cytoscape software, through the CytoHubba plugin, filters the PPI subnetwork and identifies Hub genes. Validation of the Hub genes was performed in the validation set. Immune analysis was conducted via the CIBERSORT algorithm. Transcription factor interaction and small molecule drug analyses of the Hub genes were also performed. RESULTS: Using the GSE233973 and GSE3365 datasets, 151 differentially expressed genes (DEGs) were identified. GO enrichment analysis revealed involvement in leukocyte migration and chemotaxis, response to lipopolysaccharides, response to biostimulatory stimuli, and regulation of interleukin-8 (IL-8) production. Ten Hub genes (TLR4, IL10, CXCL8, IL1B, TLR2, CXCR2, CCL2, IL6, CCR1 and MMP-9) were identified via the PPI network and Cytoscape software. Enrichment analysis of the Hub genes focused on the lipopolysaccharide response, bacterial molecular response, biostimulatory response and leukocyte movement. Validation using the GSE27411 and GSE179285 datasets revealed that MMP-9 was significantly upregulated in both the H. pylori and IBD groups. The CIBERSORT algorithm revealed immune infiltration differences between the control and disease groups of IBD patients. Additionally, the CMap database identified the top 11 small molecule compounds across 10 cell types, including TPCA-1, AS-703026 and memantine, etc. CONCLUSION: Our study revealed the co-pathogenic mechanism between H. pylori and IBD and identified 10 Hub genes related to cellular immune regulation and signal transduction. The expression of MMP-9 is significantly upregulated in both H. pylori infection and IBD. This study provides a new perspective for exploring the prevention and treatment of H. pylori infection and IBD.