Influence of landscape on the distribution of inflammatory bowel disease in England and Wales

Mycobacterium avium subspecies paratuberculosis (MAP) is the bacterial pathogen which causes Johne’s disease (JD) in animals and is reported to be significantly associated with Crohn’s disease (CD) in humans. MAP is the causative bacterial pathogen of Johne’s disease in infected animals, including ruminants. Sub-clinically and clinically infected animals shed large numbers of MAP onto pastures. Previous studies have detected MAP in pasture areas deposited by both sub-clinically and clinically infected animals with Johne’s Disease and in areas outside pastures spread by non-farmed animals. Rainfall washes the pathogen from pastures via surface water and drains into rivers, thus, providing a route for human exposure from infected cattle via potable water supplies and riverine aerosols. Based on a large UK-wide IBD survey, involving 5,452 participants, we examined whether the relative risk of CD was associated with catchment-level exposure to pastures, which support a mixture of clinically and sub-clinically MAP-infected ruminants as well as disease-free animals. We used pasture proportion and hydrological transport pathways as environmental exposure indicators. Specifically, we investigated the association between the number of CD cases relative to the population (used as an offset) and biogeographical features measured at the hydrological catchment level by fitting a Poisson regression model. Covariates comprised pasture proportion (selected as a proxy for ruminant grazing), urban proportion, monthly average temperature, monthly average precipitation and river width. The same model was fitted for ulcerative colitis (UC) to provide comparative control. A statistically significant relationship was found between the number of CD cases and pasture proportion, while the association between number of UC cases and pasture proportion was statistically insignificant. This research is the first to show an association between CD risk and the proportion of pasture at the national scale, thus, providing evidence to support the hypothesis that living within catchments with a greater proportion of pasture upon which MAP-infected animals graze may increase the likelihood of CD amongst the at-risk population.