IBD DNA Methylation

In this editorial, we comment on the article by Marangoni et al , published in the recent issue of the World Journal of Gastroenterology 2023; 29: 5618-5629, about "Diet as an epigenetic factor in inflammatory bowel disease". The authors emphasized the role of diet, especially the interaction with genetics, in promoting the inflammatory process in inflammatory bowel disease (IBD) patients, focusing on DNA methylation, histone modifications, and the influence of microRNAs. In this editorial, we explore the interaction between genetics, gut microbiota, and diet, in an only way...

DNA methylation has been implied to play a role in the immune dysfunction associated with inflammatory bowel disease (IBD) and the disease development of ulcerative colitis (UC). Changes of the DNA methylation and correlated gene expression in patient samples with inactive UC might reveal possible regulatory features important for further treatment options for UC. Targeted bisulfite sequencing and whole transcriptome sequencing were performed on mucosal biopsies from patients with active UC (UC, n = 14), inactive UC (RM, n = 20), and non-IBD patients which served as controls (NN, n = 11)...

BACKGROUND AND AIMS: Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions influenced heavily by environmental factors. DNA methylation is a form of epigenetic regulation linking environmental stimuli to gene expression changes and inflammation. Here, we investigated how DNA methylation of the TNF promoter differs between inflamed and uninflamed mucosa of IBD patients, including anti-TNF responders and non-responders. METHODS: We obtained mucosal biopsies from 200 participants (133 IBD and 67 controls) and analyzed TNF promoter methylation using bisulfite sequencing, comparing inflamed with uninflamed segments, in addition to paired inflamed/uninflamed samples from individual patients...

This work aims to investigate how smoking exerts effect on the development of inflammatory bowel disease (IBD). A prospective cohort study and a Mendelian randomization study are first conducted to evaluate the association between smoking behaviors, smoking-related DNA methylation and the risks of Crohn's disease (CD) and ulcerative colitis (UC). We then perform both genome-wide methylation analysis and co-localization analysis to validate the observed associations. Compared to never smoking, current and previous smoking habits are associated with increased CD (P = 7...

Histone methyltransferase SETDB1 (SET domain bifurcated histone lysine methyltransferase 1, also known as ESET or KMT1E) is known to be involved in the deposition of the di- and tri-methyl marks on H3K9 (H3K9me2 and H3K9me3), which are associated with transcription repression. SETDB1 exerts an essential role in the silencing of endogenous retroviruses (ERVs) in embryonic stem cells (mESCs) by tri-methylating H3K9 (H3K9me3) and interacting with DNA methyltransferases (DNMTs). Additionally, SETDB1 is engaged in regulating multiple biological processes and diseases, such as ageing, tumors, and inflammatory bowel disease (IBD), by methylating both histones and non-histone proteins...

BACKGROUND: Perinatal exposure to titanium dioxide (TiO2 ), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel disease (IBD) later in life. Here, we investigate the impact of perinatal foodborne TiO2 exposure on the intestinal mucosal function and the susceptibility to develop IBD-associated colitis. Pregnant and lactating mother mice were exposed to TiO2 until pups weaning and the gut microbiota and intestinal barrier function of their offspring was assessed at day 30 post-birth (weaning) and at adult age (50 days)...

INTRODUCTION: Ulcerative colitis (UC) is a chronic illness requiring lifelong management that could be enhanced by personalizing care using biomarkers. AREAS COVERED: The main biomarker discovery modalities are reviewed, highlighting recent results across the spectrum of applications, including diagnostics (serum anti-αvβ6 antibodies achieving an area under the curve [AUC] = 0.99; serum oncostatin M AUC = 0.94), disease activity assessment (fecal calprotectin and serum trefoil factor 3: AUC > 0...

EBV is a gammaherpesvirus strongly associated to human cancer. The virus has been shown to play a role also in inflammatory diseases, including IBD, in the context of which colon cancer more frequently arise. In this study, we show for the first time that EBV infects primary colonic epithelial cells (HCoEpC), promotes pro-inflammatory cytokine secretion and activates molecular pathways bridging inflammation and cancer, such as ERK1/2. These effects, occurring in the course of the lytic phase of the viral life cycle, led to DDR and autophagy dysregulation...

Graphical abstract [Formula: see text] Numerous environmental factors frequently emerge as primary determinants of inflammatory bowel disease (IBD). Diet is a major component of environmental factors, and the consumption of vitamins (A, B, C and D) and trace elements (calcium, iron, zinc and selenium) exerts an impact on the progression of IBD through epigenetic modifications. Intake of vitamins A, B, C and D, as well as excessive amounts of iron and calcium, can modulate the condition of IBD by regulating the levels of DNA methylation, histone acetylation and miRNA...

DNA methylation functions as a repressive epigenetic mark that can be reversed by the Ten-eleven translocation (TET) family of DNA dioxygenases that sequentially oxidize 5-methylcytosine into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be excised by DNA base-excision repair factors leading to unmodified cytosines. TET enzymes were recently implicated as potential risk factors for inflammatory bowel disease (IBD), but the contribution of TET-mediated DNA oxidation to intestinal homeostasis and response to environmental stressors are unknown...

BACKGROUND AND AIMS: Anti-TNF treatment failure in patients with inflammatory bowel disease (IBD) is common and frequently related to low drug concentrations. In order to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy, we sought to define epigenetic biomarkers in whole blood at baseline associated with anti-TNF drug concentrations at week 14. METHODS: DNA methylation from 1,104 whole blood samples from 385 patients in the Personalised Anti-TNF Therapy in Crohn's disease (PANTS) study were assessed using the Illumina EPIC Beadchip (v1...

INTRODUCTION: Predictive biomarkers for treatment efficacy of ulcerative colitis (UC) treatments are lacking. Here, we performed a longitudinal study investigating the association and potential predictive power of genome-wide peripheral blood (PB) DNA methylation signatures and response to tofacitinib treatment in UC. METHODS: We recruited moderate-to-severe UC patients starting tofacitinib treatment and measured PB DNA methylation profiles at baseline (T1), after 8 weeks (T2), and in a subset (n=8), after a median of 20 weeks (T3) using the Illumina Infinium HumanMethylation EPIC BeadChip...

BACKGROUND: Pinpointing genetic impacts on DNA methylation can improve our understanding of pathways that underlie gene regulation and disease risk. RESULTS: We report heritability and methylation quantitative trait locus (meQTL) analysis at 724,499 CpGs profiled with the Illumina Infinium MethylationEPIC array in 2358 blood samples from three UK cohorts. Methylation levels at 34.2% of CpGs are affected by SNPs, and 98% of effects are cis-acting or within 1 Mbp of the tested CpG...

Inflammatory bowel diseases (IBDs) are a group of chronic diseases characterized by recurring periods of exacerbation and remission. Fibrosis of the intestine is one of the most common complications of IBD. Based on current analyses, it is evident that genetic factors and mechanisms, as well as epigenetic factors, play a role in the induction and progression of intestinal fibrosis in IBD. Key genetic factors and mechanisms that appear to be significant include NOD2 , TGF-β , TLRs , Il23R , and ATG16L1 ...

BACKGROUND & AIMS: DNA methylation alterations may provide important insights into gene-environment interaction in cancer, aging and complex diseases such as inflammatory bowel disease (IBD). We aim firstly to determine whether the circulating DNA methylome in patients requiring surgery may predict Crohn's disease (CD) recurrence following intestinal resection; and secondly to compare the circulating methylome seen in patients with established CD with that we had reported in a series of inception cohorts...

BACKGROUND: SLCO2A1 encodes a prostaglandin (PG) transporter, and autosomal recessive pathogenic variants of this gene cause chronic enteropathy associated with SLCO2A1. It is unclear whether a heterozygous pathogenic variant of SLCO2A1 has a role in the pathogenesis of other types of inflammatory bowel disease (IBD). In this study, we investigated the possible involvement of a local epigenetic alteration in SLCO2A1 in patients with a heterozygous pathogenic variant. METHODS: We conducted whole-exome sequencing of samples from 2 sisters with suspected monogenic IBD...

BACKGROUND: The development of Crohn's disease (CD) involves immune cell signaling pathways regulated by epigenetic modifications. Aberrant DNA methylation has been identified in peripheral blood and bulk intestinal tissue from CD patients. However, the DNA methylome of disease-associated intestinal CD4 + lymphocytes has not been evaluated. MATERIALS AND METHODS: Genome-wide DNA methylation sequencing was performed from terminal ileum CD4 + cells from 21 CD patients and 12 age and sex matched controls...

Epigenetic modification is a complex process of reversible and heritable alterations in gene function, and the combination of epigenetic and metabolic alterations is recognized as an important causative factor in diseases such as inflammatory bowel disease (IBD), osteoarthritis (OA), systemic lupus erythematosus (SLE), and even tumors. Mesenchymal stem cell (MSC) and MSC-derived exosome (MSC-EXO) are widely studied in the treatment of inflammatory diseases, where they appear to be promising therapeutic agents, partly through the potent regulation of epigenetic modifications such as DNA methylation, acetylation, phosphorylation, and expression of regulatory non-coding RNAs, which affects the occurrence and development of inflammatory diseases...

BACKGROUND: Colorectal cancer (CRC) is a highly prevalent cancer, and the global healthcare system bears a significant burden due to its incidence. Modulating the gut microbiota is a promising approach to enhance the efficacy of CRC treatment and reduce its adverse effects. The causal relationship between specific microorganisms' presence and CRC development has been widely validated. However, few studies have investigated this relationship using bibliometric methods. Therefore, this study analyzed the research hotspots and trends in human gut microbiology and CRC over the last two decades from a bibliometric perspective...

BACKGROUND: Colitis-associated cancer (CAC) is one of the most severe complications of inflammatory bowel disease (IBD), which has caused a worse survival rate in IBD patients. Although the exact aetiology and pathogenesis of CAC are not completely elucidated, evidence indicates that non-coding RNAs are closely involved and play a key role. METHODS: This review aims to summarise the major findings of non-coding RNAs in the development of CAC and present the potential mechanistic links between non-coding RNAs and CAC pathogenesis...