The role of cellular methylation in IBD

The intestinal epithelium serves as a barrier from foreign food material and harmful bacteria. When this barrier is compromised in genetically susceptible individuals, the immune system becomes exposed, resulting in chronic inflammation.

It is now appreciated that inflammatory responses in IBD are accompanied by striking shifts in tissue metabolism, including key metabolites involved in cellular methylation.  Methylation reactions are a critical component of the control of gene expression, as well as protein function.  We have demonstrated that inhibition of cellular methylation exacerbates disease in mouse models of colitis indicating that these processes are protective of the epithelium.  Additionally, our results indicate that epigenetic mechanisms play a role in the epithelial responses during inflammation.

Guided by these studies, we hypothesize that inflammation-induced epigenetic alterations modify gene expression as an integral aspect of epithelial inflammatory pathways and that alteration of DNA methylation represents a protective mechanism for the epithelium during intestinal inflammation.