Abstract
The association between long-term air pollution exposure and inflammatory bowel disease (IBD) remains inconclusive. A total of 133,261 participants from the UK Biobank, a prospective cohort were included. Incident IBD cases were ascertained from the administrative database of the National Health Services. Air pollution exposure (PM2.5, PM10, NO2 and NOx) at participants’ residential addresses was estimated by spatio-temporal models. Cox regression models were used to assess the associations between air pollution and IBD. Metabolic signatures were constructed by summing selected plasma metabolites associated with air pollution through elastic net regression. Afterwards, mediation analyses were conducted to investigate the potential mediation of metabolic signatures on the air pollution-IBD associations. During a mean follow-up of 11.61 years (SD: 1.78), 824 incident IBD cases were identified. Long-term exposure to PM2.5, PM10, NO2, and NOx was positively associated with IBD risk: hazard ratios were 1.019 (95 % CI: 0.933, 1.112), 1.033 (95 % CI: 0.942, 1.132), 1.112 (95 % CI: 1.026, 1.227), and 1.121 (95 % CI: 1.028, 1.223), respectively. As PM2.5 and PM10 were not significantly associated with incident IBD, subsequent metabolic analysis was only conducted for NO2 and NOx. The metabolic signatures for NO2 and NOx included 26 and 18 metabolites (mostly related to amino acids, glucose metabolism, and lipid metabolism), respectively. The significant associations of NO2 and NOx with incident IBD were explained by their metabolic signatures (mediation: 10.13 % (95 % CI: 4.56 %, 42.87 %) and 9.17 % (95 % CI: 3.87 %, 38.64 %), respectively). Our findings suggest that long-term air pollution exposure could increase IBD risk, potentially through mediation by metabolic changes.