Causal Relationship Between 91 Inflammatory Factors and Gastritis: A Two-Sample Bidirectional Mendelian Randomization Study

Introduction: Emerging evidence from recent pathological investigations has demonstrated that inflammation plays a critical role in the progression of gastrointestinal diseases. However, the causal relationships between inflammation and gastritis still lack further validation. Methods: Mendelian Randomization (MR) was used to evaluate the causal effects of inflammatory factors on gastritis. The datasets of 91 inflammatory factors were obtained from the Genome-Wide Association Study (GWAS) database, and the genetic datasets of Acute Gastritis (AG) and Chronic Gastritis (CG) were obtained from the GWAS database and the FinnGen database, respectively. Heterogeneity and pleiotropy were assessed with Cochran's Q test and MR-Egger's intercept test, respectively. Results: After accounting for heterogeneity and horizontal pleiotropy, MR analysis identified Axin-1, C-X-C motif chemokine 10 (CXCL10), and Fms-related tyrosine kinase 3 ligand to be significantly associated with acute gastritis, while linking CXCL10, glial cell line-derived neurotrophic factor, Leukemia Inhibitory Factor Receptor (LIFR), hepatocyte growth factor, and fibroblast growth factor 19 to chronic gastritis. Furthermore, reverse MR analysis revealed that CG could significantly downregulate the levels of Interleukin-2 receptor subunit beta, Interleukin-15 receptor subunit alpha, Interleukin-20 receptor subunit alpha, LIFR, and Interleukin-1-alpha. Discussion: This study found that AG and CG were associated with distinct inflammatory factors and that CG could reverse the levels of inflammatory factors. CXCL10 and LIFR may be potential biomarkers for gastritis. Conclusion: This study systematically identified causal relationships between inflammatory factors and gastritis. The identified inflammatory factors offer new insights into potential targets for gastritis.