Epigenetics in IBD: a conceptual framework for disease pathogenesis

Abstract

The global incidence and prevalence of paediatric inflammatory bowel disease (IBD) is increasing, with a notable emergence in developing countries with historically low rates. This suggests that environmental and epigenetic factors may play an important role in the pathogenesis and progression of IBD. Epigenetics refers to the study of biological mechanisms that result in a change of phenotype, without an change in the underlying DNA sequence. Epigenetic mechanisms drive many biological processes that occur in health, such as development and ageing, and are also implicated in disease, including cancer and other inflammatory diseases. Importantly, identification of cell-type-specific epigenetic mechanisms could lead to the identification of molecular disease subtypes allowing a personalised treatment approach. In this short review, we provide a summary of epigenetic mechanisms operative in mammals, and their potential involvement in IBD pathogenesis. Furthermore, we discuss key challenges associated with investigating epigenetics in IBD and provide potential strategies to overcome these, such as through the use of ‘omics’ and organoid technologies.

Interaction between diet and genetics in patients with inflammatory bowel disease

“…The term epigenetic was studied in the middle of the 19 th century by biologist British Conrad Hall Waddington[ 2 ], to describe the interaction between genes and environment that allows the emergence of phenotypes. The first publication about epigenetics and IBD was in 1996[ 3 ].…”

“…In patients with IBD, the most studied modifications have been DNA-methylation and noncoding RNA that may be induced by smoking and diet[ 4 , 5 ]. Interestingly, this DNA-methylation is a process that is dependent on cofactors dietary such as substrates and nutrients (folate, vitamins B12, D, and others)[ 2 ] and is associated with inflammation, microbiota composition, and microRNAs (miRNAs) which can affect IBD by interfering with T cells differentiation[ 6 ]. Marangoni et al [ 1 ] provided an elegant review of the role of DNA methylation in IBD and its consequences to the inflammatory process.…”

“…In the recent review, Natasha and Zilbauer[ 2 ] claim that genetic changes may account for modest percentages of IBD, while epigenetic factors could potentially have contributed to the increase in the incidence of disease in recent decades and could be a key role of environmental factors in IBD pathogenesis.…”

“…It is worth highlighting that factors determining the degree of cellular epigenetic changes include the type of environmental factors and duration[ 2 ]. Some authors consider three critical periods during which the environment may favor the onset of the IBD: In utero, or the early postnatal phase (during gut microbiota colonization), and just before the disease onset[ 2 , 7 ].…”

Immunoepigenetic Regulation of Inflammatory Bowel Disease: Current Insights into Novel Epigenetic Modulations of the Systemic Immune Response

“…Thus, environmental factors and their relationship to the genome-epigenome are considered primary causes of IBD [ 7 ]. In this context, precision medicine has become an important issue in clinical practice [ 16 ], in which the definition of the role of epigenetics in IBD can provide new directions toward achieving better therapies for and monitoring IBD [ 17 , 18 ].…”