High-Dimensional DNA Methylation Mediates the Effect of Smoking on Crohn’s Disease

Wang, Tingting; Xia, Pingtian; Su, Ping

doi:10.3389/fgene.2022.831885

Cited by 6 publications

(3 citation statements)

References 50 publications

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“…Regarding smoking-induced DNA methylation, a meta-analysis performed by Joehanes and colleagues highlighted various genome-wide association studies showing that smoking-induced genes differentially methylated are enriched for variants associated with smoking-related diseases, including IBD, CD and UC [ 210 , 215 , 216 ]. The findings suggest that changes in methylation of the BCL3 , FKBP5 , AHRR and GPR15 genes are involved in the mechanism by which smoking increases the risk of CD [ 217 , 218 ].…”

Section: Resultsmentioning

confidence: 99%

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

Vieujean

Caron

Haghnejad

et al. 2022

IJMS

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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.

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Section: Resultsmentioning

confidence: 99%

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

Vieujean

Caron

Haghnejad

et al. 2022

IJMS

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“…Studies implicating epigenetic alterations as the link between smoking and health outcomes are rapidly growing. Multiple studies have identified changes in DNAm as mediators between smoking and health outcomes both in adult smokers 13,62 and in offspring exposed to CS in utero 23,[63][64][65] . DNAm patterns resulting from smoking may be the key to developing strategies to counteract or prevent its detrimental effects.…”

Section: Discussionmentioning

confidence: 99%

Novel DNA methylation changes in mouse lungs associated with heavy smoking

Onuzulu,

Lee,

Basu

et al. 2023

Preprint

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Smoking is a potent cause of asthma, chronic obstructive pulmonary disease (COPD) and many other health defects, and changes in DNA methylation (DNAm) have been identified as a potential link between smoking and these health outcomes. However, most links between smoking and DNAm have been made using blood and other easily accessible tissues in humans, while evidence from more directly affected tissues such as the lungs is greatly lacking. Here, we identified DNAm patterns which are altered by smoking directly in the lungs. We used a well-established mouse model to measure the effects of heavy smoking first on lung phenotype immediately after smoking and then after a period of smoking cessation. Next, we determined whether our mouse model could recapitulate previous DNAm patterns observed in smoking humans by measuring DNAm at a candidate gene responsive to cigarette smoke (CS),Cyp1a1.Finally we carried out epigenome-wide DNAm analyses using the newly released Illumina mouse methylation microarrays. Our results recapitulate some of the phenotypes and DNAm patterns observed in human studies but reveal 32 differentially methylated genes specific to the lungs which have not been previously associated with smoking. The affected genes are known to be involved in nicotine dependency, tumorigenesis and metastasis, immune cell dysfunction, lung function decline, and COPD. This research emphasizes the need to study CS-mediated DNAm signatures in directly affected tissues like the lungs, as that may be essential in understanding mechanisms underlying CS-mediated health outcomes.

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“…The epigenome is thought to facilitate the interaction between genes and the environment, resulting in diverse phenotypes in cells or organisms with identical genomes. The influence of environmental factors, such as smoking, diet, physical activity and vitamin D supplementation, has been studied in clinical and preclinical studies on CD [ 84 , 85 , 86 ].…”

Section: Epigenomicsmentioning

confidence: 99%

Are We Ready to Reclassify Crohn’s Disease Using Molecular Classification?

Kamal,

Parkash,

Beattie

et al. 2023

JCM

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Crohn’s disease (CD) is a type of inflammatory bowel disease. The number of IBD cases worldwide was estimated to be 4.9 million in 2019. CD exhibits heterogeneity in clinical presentation, anatomical involvement, disease behaviour, clinical course and response to treatment. The classical description of CD involves transmural inflammation with skip lesions anywhere along the entire gastrointestinal tract. The complexity and heterogeneity of Crohn’s disease is not currently reflected in the conventional classification system. Though the knowledge of Crohn’s pathophysiology remains far from understood, the established complex interplay of the omics—genomics, transcriptomics, proteomics, epigenomics, metagenomics, metabolomics, lipidomics and immunophenomics—provides numerous targets for potential molecular markers of disease. Advancing technology has enabled identification of small molecules within these omics, which can be extrapolated to differentiate types of Crohn’s disease. The multi-omic future of Crohn’s disease is promising, with potential for advancements in understanding of its pathogenesis and implementation of personalised medicine.

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High-Dimensional DNA Methylation Mediates the Effect of Smoking on Crohn’s Disease

Cited by 6 publications

References 50 publications

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

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

Novel DNA methylation changes in mouse lungs associated with heavy smoking

Are We Ready to Reclassify Crohn’s Disease Using Molecular Classification?

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