Role of epigenetic mechanisms in inflammatory bowel disease

Abstract: Epigenetic mechanisms maintain gene expression states within a cell and through cellular generations and involve DNA methylation and chromatin changes, such as histone modifications. These mechanisms play roles in inflammatory processes. Here we review recent advances about what we know about their impact in inflammatory bowel disease (IBD). The incidence and prevalence of IBD have significantly increased in recent decades, establishing it as one of the most common gastrointestinal disorders. Lifestyle changes, including dietary factors, have been identified as potential contributors to this phenomenon. Although the heritability of IBD cannot be solely attributed to common genetic variants, their examination has shed light on the involvement of epigenetic and chromatin factors, such as DNMT3A and SP140, in the development of IBD. Studies focusing on SP140 have provided a paradigm by demonstrating the association between genetic alterations in this gene and changes in chromatin structure, gene expression, and the composition of the microbiome, ultimately resulting in abnormal inflammation. Genetic deletion coupled to experimental colitis studies in mice have highlighted roles of additional important factors linked to DNA methylation, MBD2 and UHRF1, and histone methylation, such as SETD2, in regulating the inflammatory processes in the gut. Further research is needed to investigate how environmental factors contribute to the predisposition of IBD through epigenetic mechanisms. This line of inquiry holds the potential to pave the way for new intervention strategies.