S1880 Causal Effects of Various Particulate Matter/Air Pollution on Inflammatory Bowel Disease: Insights From a Systematic Review and Meta-Analysis of Mendelian Randomization Studies

Introduction: The incidence of inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and Ulcerative colitis (UC), continues to rise globally, affecting up to 2.4 million people in the United States alone. Environmental factors, including exposure to particulate air pollution (PM2.5), have been implicated in IBD pathogenesis through pro-inflammatory cytokine release and epigenetic modifications. However, observational studies examining this relationship have shown inconsistent findings, often limited by confounding and reverse causality. Mendelian Randomization (MR) is a method that utilizes genetic variants to study disease causation. This meta-analysis synthesizes MR studies evaluating the causal association between PM2.5 exposure and the risk of IBD. Methods: We systematically searched PubMed, EMBASE, and Google Scholar for studies evaluating the association between PM2.5 exposure and IBD, including CD, UC, or unclassified IBD using MR until May 2025. Eligible studies utilized 2-sample MR designs and reported causal estimates using the inverse-variance weighted (IVW) method. Only IVW-derived odds ratios (ORs) were included in the quantitative synthesis. A random-effects meta-analysis model was applied to pool effect estimates. Heterogeneity across studies was assessed using the I² and Tau² statistics. Results: A total of 6 studies were included in our final analysis. The pooled OR for the association between PM2.5 and overall IBD was 1.01 (95% CI: 0.99–1.02; P = 0.27), with substantial heterogeneity (I² = 72%). Subgroup analysis showed no significant association for UC (OR = 1.02; 95% CI: 0.99–1.05; I² = 78%) or CD (OR = 1.00; 95% CI: 1.00–1.00; I² = 0%). However, 2 studies examining unclassified IBD demonstrated a significant association (OR = 1.54; 95% CI: 1.14–2.09; P = 0.005; I² = 0%). Sensitivity analyses revealed no influential outliers. Conclusion: This meta-analysis of MR studies found no evidence supporting a causal relationship between PM2.5 exposure and risk of UC or CD. A statistically significant association was observed for unclassified IBD, though interpretation is limited by the small number of contributing studies. Further large-scale MR studies and stratified analysis are warranted to explore potential subtype-specific and population-specific effects of air pollution on IBD development.