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

[BACKGROUND] Helicobacter pylori ( H. pylori ), a Group 1 carcinogen, is linked to gastritis, gastric cancer, and extragastric diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS), and systemic sclerosis (SSc). Despite these epidemiological associations, the molecular mechanisms underlying their comorbidity remain unclear.

[MATERIALS AND METHODS] Integrated transcriptomics 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 defense (in SLE and SSc), and dysregulated Toll-like/NOD-like receptor signaling. 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.