The Molecular Interplay Between Helicobacter pylori Infection and Ulcerative Colitis: Unraveling Shared Biomarkers
Min Zhu1,2,3,4, Xiao Li5, Xinyuan Huang1,2,3,4
1Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Background:
Ulcerative colitis (UC) and Helicobacter pylori (H. pylori) infection show an intriguing inverse epidemiological association, but the underlying molecular mechanisms remain unclear, with emerging evidence suggesting H. pylori may modulate colonic inflammation via systemic immune regulation.
Methods:
We used bioinformatics approaches, including gene set enrichment analysis (GSEA), differential expression analysis, functional enrichment (GO/KEGG), protein-protein interaction (PPI) networks, upstream regulatory molecule prediction, and immune infiltration characterization, to analyze gene expression datasets from UC and H. pylori-infected samples, aiming to identify the interconnections and regulatory networks between these two conditions.
Results:
GSEA identified 53 shared pathways, primarily innate immune response pathways (e.g., TLR/NLR signaling, NF-κB/IL-17 cascades). We found 243 co-differentially expressed genes enriched in leukocyte chemotaxis, cytokine activity, and extracellular matrix organization. Six hub genes (CXCL8, IL1B, MMP9, CXCL1, IFNG, CXCL9) were validated as robust diagnostic markers (AUC > 0.815 for both conditions). Immune landscape analysis revealed pan-infiltration of immune cells in H. pylori-infected tissues and shared dysregulated immune cells in UC tissues, with hub genes positively correlated with immune cell infiltration in both. We also identified regulatory miRNAs (e.g., miR-204-5p) and transcription factors (FOXC1, YY1) modulating these hub genes.
Conclusion:
This study uncovers shared immune-mediated pathways and hub genes linking H. pylori infection to UC, establishing a molecular framework. These hub genes and regulatory networks may serve as diagnostic biomarkers and therapeutic targets, highlighting the need to investigate H. pylori-driven immune modulation in UC pathogenesis.
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