Impact of the Exposome on the Epigenome in Inflammatory Bowel Disease Patients and Animal Models

Abstract

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that encompass two main phenotypes, namely Crohn’s disease and ulcerative colitis. These conditions occur in genetically predisposed individuals in response to environmental factors. Epigenetics, acting by DNA methylation, post-translational histones modifications or by non-coding RNAs, could explain how the exposome (or all environmental influences over the life course, from conception to death) could influence the gene expression to contribute to intestinal inflammation. We performed a scoping search using Medline to identify all the elements of the exposome that may play a role in intestinal inflammation through epigenetic modifications, as well as the underlying mechanisms. The environmental factors epigenetically influencing the occurrence of intestinal inflammation are the maternal lifestyle (mainly diet, the occurrence of infection during pregnancy and smoking); breastfeeding; microbiota; diet (including a low-fiber diet, high-fat diet and deficiency in micronutrients); smoking habits[ vitamin D and drugs (e.g., IBD treatments, antibiotics and probiotics). Influenced by both microbiota and diet, short-chain fatty acids are gut microbiota-derived metabolites resulting from the anaerobic fermentation of non-digestible dietary fibers, playing an epigenetically mediated role in the integrity of the epithelial barrier and in the defense against invading microorganisms. Although the impact of some environmental factors has been identified, the exposome-induced epimutations in IBD remain a largely underexplored field. How these environmental exposures induce epigenetic modifications (in terms of duration, frequency and the timing at which they occur) and how other environmental factors associated with IBD modulate epigenetics deserve to be further investigated.

The dietary inflammatory index and its association with the prevalence of hypertension: A cross-sectional study

“…( 10 ) in 2014. DII has been validated that it can reflect the levels of systemic inflammation and closely associated with the expressions of blood inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 ( 11 , 12 ). At present, DII has already been widely used to explore the roles of diet-induced inflammation in the occurrence and development of various diseases ( 13 – 15 ).…”

Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn’s Disease Patients through Epigenetic Changes

“…Changes in methylation patterns can have far-reaching consequences for health [ 41 , 42 ]. Cigarette smoking altered the methylome of ASCs from patients with CD.…”

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

“…Another factor to consider, due to its important epigenetic influence and relation to IBD, is vitamin D ( Figure 2 ), which has a role as an immune modulator by increasing FoxP3 and IL-10 and suppressing the inflammatory cytokines IL-17, IFN-γ, IL-21, and IL-22 [ 28 , 41 , 41 ]. Low blood vitamin D levels have been linked to the risk of relapse and exacerbation in IBD [ 41 , 42 ]. Vitamin D can be regulated by histone modification, which has been considered one of the most important epigenetic mechanisms.…”