DNA methylation in inflammatory bowel disease and beyond

Abstract

Inflammatory bowel disease (IBD) is a consequence of the complex, dysregulated interplay between genetic predisposition, environmental factors, and microbial composition in the intestine. Despite a great advancement in identifying host-susceptibility genes using genome-wide association studies (GWAS), the majority of IBD cases are still underrepresented. The immediate challenge in post-GWAS era is to identify other causative genetic factors of IBD. DNA methylation has received increasing attention for its mechanistical role in IBD pathogenesis. This stable, yet dynamic DNA modification, can directly affect gene expression that have important implications in IBD development. The alterations in DNA methylation associated with IBD are likely to outset as early as embryogenesis all the way until old-age. In this review, we will discuss the recent advancement in understanding how DNA methylation alterations can contribute to the development of IBD.

Keywords: Intestinal inflammation, Crohn’s disease, Colitis, DNA methyltransferase, Epi-therapy

Core tip: This review discuss the recent research advancement in the area of DNA methylation during the pathogenesis of inflammatory bowel disease (IBD) and IBD-associated cancer, with a focus on highlighting major players mediating DNA methylation alterations during IBD development. Temporal and spatial differential DNA methylation status that contributes to the disease, as well as epi-therapy treatment options for IBD patients, are also discussed. This emerging information will have important clinical significance, especially so in this post-genome-wide association studies era of IBD research.