Large-scale plasma proteomics reveals bidirectional associations between sleep patterns and inflammatory bowel disease: a prospective cohort study

Abstract Background Sleep disturbances are common in individuals with inflammatory bowel disease (IBD) and may worsen its progression. This study investigates the bidirectional association between unhealthy sleep and IBD and explores proteomic mechanisms underlying this relationship. Methods Data from 381,228 UK Biobank participants were analyzed to calculate adjusted odds ratios (ORs) for prevalent IBD and hazard ratios (HRs) for IBD incidence in relation to sleep patterns. A subset of 40,392 participants underwent plasma proteomic profiling, where differential expression analysis and weighted gene co-expression network analysis (WGCNA) identified key protein modules. A prognostic risk model for IBD was developed using least absolute shrinkage and selection operator (LASSO)-Cox regression. Results At baseline, 26.4% of participants exhibited unhealthy sleep, which was significantly associated with higher odds of prevalent IBD (OR = 1.250, 95% CI 1.165–1.340, p < 0.001) and an increased risk of developing IBD (HR = 1.237, 95% CI 1.136–1.348, p < 0.001). Proteomic profiling revealed 182 differentially expressed proteins common to both unhealthy sleep and IBD, with WGCNA identifying modules enriched in pathways related to cell activation, chemotaxis, and amino acid and organic acid metabolism. The proteomic risk model achieved an AUC of 0.81 for predicting 2-year IBD onset. Participants with both unhealthy sleep and high proteomic risk scores had a markedly increased risk of incident IBD (HR = 3.370, 95% CI 2.300–4.938, p < 0.001). Conclusions Unhealthy sleep and IBD are bidirectionally linked, with inflammatory and metabolic processes mediating this association. These findings highlight potential biomarkers and therapeutic targets, underscoring the importance of integrating sleep assessments into IBD management strategies.