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

TL;DR

This study finds that poor sleep and inflammatory bowel disease (IBD) influence each other, with shared proteins suggesting common biological pathways that could help predict and manage IBD.

Contribution

The study identifies bidirectional links between sleep patterns and IBD, along with a proteomic risk model for predicting IBD onset.

Findings

Unhealthy sleep is associated with increased odds and risk of IBD (OR=1.250, HR=1.237).

182 proteins are differentially expressed in both unhealthy sleep and IBD, linked to inflammation and metabolism.

A proteomic risk model predicts IBD onset with an AUC of 0.81, with high risk scores and poor sleep tripling IBD risk (HR=3.370).

Abstract

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.

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.

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).

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.

The online version contains supplementary material available at 10.1186/s12916-025-04539-4.

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