DOP039 Dietary methyl group donor intake alleviates the susceptibility to inflammatory bowel disease influenced by environmental pollution in a prospective cohort study
Authors: Dan L , Fu T , Ruan X , Wang X , Chen J 
Published: January 2025

Abstract

Background
Both genetic and environmental factors play crucial roles in individual susceptibility to inflammatory bowel disease (IBD) [1], though its exact etiology remains unclear. Multiple studies have identified environmental pollutants, such as cigarette smoke and fine particulate matter, as significant risk factors for IBD [2, 3]. Chronic exposure to air pollution alters DNA methylation patterns, with a typically long-term hypomethylated status. Our previous study also found that smoking can lead to susceptibility to IBD by affecting the methylation levels of key genes [2].
Moreover, DNA methylation, as an epigenetic mechanism, has been implicated in the pathogenesis of IBD. The intake and quality of dietary methyl group donors (MGDs) directly affects the methylation process in vivo, potentially modulating the risk of developing IBD. Therefore, the present study explored the effect of dietary MGDs on the development of IBD and whether dietary MGDs intake is beneficial in modulating the susceptibility to IBD influenced by environmental pollution.

Methods
We included 186,195 IBD-free participants at baseline with available dietary information from UK Biobank. Dietary MGDs intake was aggerated by the z-score of methionine, folate, choline, betaine intake by 24h dietary recalls. Smoking behavior and intensity were ascertained via self-report questionnaires. Susceptibility to air pollution was estimated by summing up the exposure to four air pollutant (PM2.5, PM10, NOx, NO2) weighted by effect size on liability to IBD [3, 4]. Diagnosis of IBD were determined by at least two health-related records in national registries. Cox proportional hazard models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results
During a mean follow-up of 10.8 years, we identified 139 and 285 incident cases of CD and UC. We found that individuals with the highest quintiles of dietary MGDs have a significant reduction in risk of CD (HR 0.50, 95% CI 0.28-0.90, P=0.021; P-trend=0.018) and UC (HR 0.62, 95% CI 0.40-0.96, P=0.034; P-trend=0.022) compared to those in the lowest quintile (Figure 1). The associations between dietary MGD and CD were more pronounced in individuals with smoking history (HR 0.66, 95% CI 0.51-0.86), who smoke more than 20 pack-years (HR 0.63, 95% CI 0.45-0.86), who were exposed to high air pollution (HR 0.58, 95% CI 0.37-0.91) than individuals without smoking history, who smoke less than 20 pack-years, who exposed to lower air pollution (all P-interaction&lt;0.05, Figure 4).

Conclusion
This study demonstrates the potential of dietary methyl donors for the prevention of IBD and provides more precise nutritional intervention strategies for populations affected by smoking and air pollution problems.

References
[1] Sun Y, Yuan S, Chen X, et al. The Contribution of Genetic Risk and Lifestyle Factors in the Development of Adult-Onset Inflammatory Bowel Disease: A Prospective Cohort Study. Am J Gastroenterol. 2023;118(3):511-522. doi:10.14309/ajg.0000000000002180
[2] Zhang H, Kalla R, Chen J, et al. Altered DNA methylation within DNMT3A, AHRR, LTA/TNF loci mediates the effect of smoking on inflammatory bowel disease. Nat Commun. 2024;15(1):595. Published 2024 Jan 18. doi:10.1038/s41467-024-44841-y
[3] Chen J, Zhang H, Fu T, et al. Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III region. EBioMedicine. Published online November 12, 2024. doi:10.1016/j.ebiom.2024.105443
[4] Chen J, Dan L, Sun Y, et al. Ambient Air Pollution and Risk of Enterotomy, Gastrointestinal Cancer, and All-Cause Mortality among 4,708 Individuals with Inflammatory Bowel Disease: A Prospective Cohort Study. Environ Health Perspect. 2023;131(7):77010. doi:10.1289/EHP12215