Large-scale plasma proteomics reveals bidirectional associations between sleep patterns and inflammatory bowel disease: a prospective cohort study
File(s)
Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2026-01-12
Date Acceptance
2025-11-20
Citation
BMC Medicine, 2026, 24
ISSN
1741-7015
Publisher
BMC
Journal / Book Title
BMC Medicine
Volume
24
Copyright Statement
© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1186/s12916-025-04539-4
Subjects
Le
K.
Liu
Y.
Bai
R. et al. Large-scale plasma proteomics reveals bidirectional associations between sleep patterns and inflammatory bowel disease: a prospective cohort study
Publication Status
Published
Article Number
18
Date Publish Online
2025-12-05