Background and Aims
Incidence of Crohn's disease(CD) is increasing worldwide. Previous studies suggest that exposure to air pollutants may contribute to the risk of CD. We aimed to investigate the association of exposure to air pollution on the risk of CD and known biomarkers of gut inflammation, gut barrier function, and gut microbiome involved in CD pathogenesis.

Methods
In total, 2,256 healthy first-degree relatives of patients with CD from Canadian sites of the CCC-GEM project, prospectively followed until 2021 were included. Baseline biomarkers included gut permeability measured by urinary fractional excretion ratio of lactulose-to-mannitol(LMR), fecal calprotectin(FCP), and stool microbiome measured by 16S rRNA sequencing. Air pollutant exposure was estimated from the Canadian National Air Pollution Surveillance Database from subject postal codes at recruitment, using the inverse distance weighting. We defined the average pollutant exposure for short-term over three months or long exposure over the twelve-month period prior to recruitment. An additive Cox proportional hazards model, evaluated the association between individual pollutants and CD risk. Associations between pollutants and CD risk biomarkers were assessed using Generalized Estimating Equation models and adjusted for age, sex, air pollutant seasonality (based on month of recruitment), familial income, and multiplex family. Significance was set at p<0.05, and false discovery rate (q) correction was applied for microbiome analysis.

Result
Short-term exposure to particulate matter (PM) smaller than 10µm (PM₁₀) had a significant non-linear association with CD onset (p=0.01), increasing CD risk at both low and high levels. Short-term exposure to PM₁₀ was negatively associated with gut barrier function (β=-0.05, p=7.6×10^-4), but positively associated with elevated FCP (β=0.05, p=0.04). Subjects exposed to short and long term PM₁₀and to other pollutants including carbon monoxide (CO), nitric oxide, nitric dioxide (NO2), small particulate matter <2.5µm (PM_2.5), and sulfur dioxide (SO2), showed significant microbial compositional shifts(beta diversity). Long-term exposure to individual pollutants was associated with selective microbial taxa: CO with Dorea relative abundance (β=-0.14, q=0.02); NO2 with Bifidobacterium (β=0.002, q=0.04), Ozone with Blautia (β=0.002, q=0.03), PM_2.5with Bacteroides (β=-0.008, q=0.03), SO2 with Coprococcus and Faecalibacterium (β=-0.01, q=0.03; β=-0.01, q=0.04 respectively).

Conclusion
Short term air pollutant exposure to PM10 was associated with risk of CD. Short-term exposure to pollutants was associated with markers of gut inflammation and gut barrier function, whereas long-term exposure was associated with changes in gut microbiome. These results show that air pollutants may modulate CD risk biomarkers and are involved in the risk of developing CD.

Eric Benchimol

Appearances