Metabolic mediators of the causal relationship between inflammatory bowel disease and allergic rhinitis: insights from Mendelian randomization

Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, is associated with various comorbidities, such as allergic diseases like allergic rhinitis. However, the causal relationship and potential metabolic mechanisms remain unclear. This study investigates the association between inflammatory bowel disease and allergic rhinitis, focusing on potential metabolic mediation through Mendelian randomization analysis. A two-sample Mendelian randomization analysis was conducted using datasets from European populations to evaluate the relationships between inflammatory bowel disease, Crohn's disease, ulcerative colitis, and allergic rhinitis. Additionally, 212 potential mediating metabolites were analyzed to explore metabolic mechanisms. Horizontal pleiotropy was excluded, and mediation analysis identified specific metabolites mediating these effects. Results revealed a significant association between inflammatory bowel disease, Crohn's disease, and allergic rhinitis, while ulcerative colitis showed no significant impact. Further analysis confirmed a unidirectional causal relationship from inflammatory bowel disease and Crohn's disease to allergic rhinitis. Metabolite analysis identified 91 significant metabolites, with 67 showing consistent effects. Notably, erythritol, 1-myristoyl-2-arachidonoyl-GPC, and the 3-methyl-2-oxovalerate to 4-methyl-2-oxopentanoate ratio exhibited significant mediation effects. These findings highlight a significant causal link between inflammatory bowel disease, particularly Crohn's disease, and allergic rhinitis, mediated by specific metabolites, offering new insights and potential targets for clinical interventions.