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Integrated multi-omics and molecular docking reveal shared molecular mechanisms of helicobacter pylori infection and rheumatic diseases.

Ting Cai,Xuelin Zhao,Hai Hu,Fen Wang,Minglin Zhang

Published 2025 in International Journal of Surgery

ABSTRACT

BACKGROUND Helicobacter pylori (H. pylori), a Group 1 carcinogen, is linked to gastritis, gastric cancer, and extra-gastric diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), and systemic sclerosis (SSc). Despite these epidemiological associations, the molecular mechanisms underlying their comorbidity remain unclear. MATERIALS AND METHODS Integrated multi-omics were used to identify differentially expressed genes (DEGs) shared between H. pylori and rheumatic diseases, functional enrichment analysis and molecular docking were performed, and hub genes, predicted regulatory transcription factors and small-molecule drugs were identified. RESULTS We identified DEGs shared between H. pylori infection and rheumatic diseases: namely 134 (RA), 103 (SLE), 244 (pSS), and 75 (SSc). Functional enrichment revealed the following convergent pathways across diseases: immune activation (in RA and pSS), viral defence (in SLE and SSc), and dysregulated Toll-like/NOD-like receptor signalling. Based on the highest degree scores, hub gene screening prioritized CXCL10, JUN (RA); STAT1, CXCL10, ISG15, and MX1 (SLE); PTPRC, ITGB2, CD19, STAT1 and CXCL10 (pSS); and STAT1, CXCL10, MX1, and OAS1 (SSc). Immune infiltration demonstrated disease-specific dysregulation: M1 macrophages in RA/pSS, monocytes in SLE, and T-cell subsets in SSc. Transcription factor analysis revealed STAT1, RELA, and IRFs to be key regulators, as validated in disease datasets. Drug prediction and molecular docking revealed geldanamycin (targeting IGF1R and JUN in RA), oestriol (OAS family and ISG15 in SLE), atorvastatin (CXCL10 and TLR4 in pSS), and cerivastatin (TLR4 in SSc) as potential therapeutics. CONCLUSION This study revealed the immune/viral pathways and hub genes linking H. pylori to rheumatic diseases, suggesting potential therapeutic targets.

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