The DNA methylome of inflammatory bowel disease (IBD) reflects intrinsic and extrinsic factors in intestinal mucosal cells

ABSTRACT

Abnormal DNA methylation has been described in human inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD). As other complex diseases, IBD results from the balance between genetic predisposition and environmental exposures. As such, DNA methylation may be the consequence (and potential effector) of both, genetic susceptibility variants and/or environmental signals such as cytokine exposure. We attempted to discern between these two non-excluding possibilities by performing a combined analysis of published DNA methylation data in intestinal mucosal cells of IBD and control samples. We identified abnormal DNA methylation at different levels: deviation from mean methylation signals at site and region levels, and differential variability. A fraction of such changes is associated with genetic polymorphisms linked to IBD susceptibility. In addition, by comparing with another intestinal inflammatory condition (i.e., coeliac disease) we propose that aberrant DNA methylation can also be the result of unspecific processes such as chronic inflammation. Our characterization suggests that IBD methylomes combine intrinsic and extrinsic responses in intestinal mucosal cells, and could point to knowledge-based biomarkers of IBD detection and progression.

Graphical abstract

KEYWORDS:

• DNA methylation
• inflammatory bowel disease (IBD)
• biomarkers
• coeliac disease (CeD)
• methylation quantitative trait loci (mQTLs)

Acknowledgments

We thank the patients involved in the research and all researchers that deposited their data in open repositories.

Availability of data and material

Demographic, clinical, and genomic data used in the present study have been published in open access repositories and are available to the public (Table 1). No additional datasets were generated or analyzed during the current study.

Disclosure statement

The authors declare that they have no competing interests.

Authors’ contributions

IA and HH carried out the methylation data meta-analysis; NF and JRB performed the mQTL analyses and IBD-CeD comparison; IA, HH, RD, and CG co-wrote the first draft of the manuscript; JM and HH conceived the study. All authors read, critically revised and approved the final manuscript.

Preprint

This manuscript can be accessed as a preprint version at the following link:

https://www.biorxiv.org/content/10.1101/565200v1

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales [ANRS, Reference No. ECTZ47287 and ECTZ50137]; Institut National du Cancer (FR) [PLBIO 2017] (project: T cell tolerance to microbiota and colorectal cancers), and Ligue Contre le Cancer (FR) [AAP 2018]; NF is partially funded by the Basque Department of Health [project 2018/111086].