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The DNA methylome of inflammatory bowel disease (IBD) reflects intrinsic and extrinsic factors in intestinal mucosal cells.

ABSTRACT: Abnormal DNA methylation has been described in human inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD). As other complex diseases, IBD results from the balance between genetic predisposition and environmental exposures. As such, DNA methylation may be the consequence (and potential effector) of both, genetic susceptibility variants and/or environmental signals such as cytokine exposure. We attempted to discern between these two non-excluding possibilities by performing a combined analysis of published DNA methylation data in intestinal mucosal cells of IBD and control samples. We identified abnormal DNA methylation at different levels: deviation from mean methylation signals at site and region levels, and differential variability. A fraction of such changes is associated with genetic polymorphisms linked to IBD susceptibility. In addition, by comparing with another intestinal inflammatory condition (i.e., coeliac disease) we propose that aberrant DNA methylation can also be the result of unspecific processes such as chronic inflammation. Our characterization suggests that IBD methylomes combine intrinsic and extrinsic responses in intestinal mucosal cells, and could point to knowledge-based biomarkers of IBD detection and progression.

SUBMITTER: Agliata I

PROVIDER: S-EPMC7518701 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Blockade of PLD2 Ameliorates Intestinal Mucosal Inflammation of Inflammatory Bowel Disease.

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| S-EPMC5046040 | biostudies-literature

COVID-19 Vaccination in Inflammatory Bowel Disease (IBD).

Project description:Vaccines against SARS-CoV-2 are believed to play a key role in the suppression of the COVID-19 pandemic. However, patients suffering from inflammatory bowel diseases (IBD) were excluded from SARS-CoV-2 vaccines trials. Therefore, concerns regarding vaccination efficacy and safety among those patients were raised. Overall, vaccination is well tolerated in the IBD population, and different gastroenterological societies recommend vaccinating patients with IBD at the earliest opportunity to do so. Nevertheless, very little is known about the safety of COVID-19 vaccines in special IBD populations such as pregnant and breastfeeding women or pediatric patients, and further research on this matter is crucial. The available data on vaccine efficacy are promising and show high seroconversion rates in IBD patients on different immune-modifying therapies. However, patients treated with high doses of systemic corticosteroids, infliximab or infliximab and immunomodulators may have a blunted response to the vaccination. The data on COVID-19 vaccination willingness among patients with IBD are conflicting. Nevertheless, vaccine effectiveness and safety are reported to be the most common reasons for hesitancy. This review examines the effectiveness and safety of COVID-19 vaccines and describes vaccination willingness and the reasons for potential hesitancy among patients with IBD.

| S-EPMC9104993 | biostudies-literature

Extrinsic inflammatory, but not intrinsic oligodendroglial factors contribute to oligodendroglial differentiation block in multiple sclerosis

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2020-09-04 | PXD016043 | Pride

Colonic mucosal and serum expression of microRNAs in canine large intestinal inflammatory bowel disease.

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| S-EPMC7035774 | biostudies-literature

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| S-EPMC4256710 | biostudies-other

Nutritional Assessment in Inflammatory Bowel Disease (IBD)-Development of the Groningen IBD Nutritional Questionnaires (GINQ).

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| S-EPMC6893781 | biostudies-literature

A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease.

Project description:Abnormalities of the intestinal microbiota are implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), two spectra of inflammatory bowel disease (IBD). However, the high complexity and low inter-individual overlap of intestinal microbial composition are formidable barriers to identifying microbial taxa representing this dysbiosis. These difficulties might be overcome by an ecologic analytic strategy to identify modules of interacting bacteria (rather than individual bacteria) as quantitative reproducible features of microbial composition in normal and IBD mucosa. We sequenced 16S ribosomal RNA genes from 179 endoscopic lavage samples from different intestinal regions in 64 subjects (32 controls, 16 CD and 16 UC patients in clinical remission). CD and UC patients showed a reduction in phylogenetic diversity and shifts in microbial composition, comparable to previous studies using conventional mucosal biopsies. Analysis of weighted co-occurrence network revealed 5 microbial modules. These modules were unprecedented, as they were detectable in all individuals, and their composition and abundance was recapitulated in an independent, biopsy-based mucosal dataset 2 modules were associated with healthy, CD, or UC disease states. Imputed metagenome analysis indicated that these modules displayed distinct metabolic functionality, specifically the enrichment of oxidative response and glycan metabolism pathways relevant to host-pathogen interaction in the disease-associated modules. The highly preserved microbial modules accurately classified IBD status of individual patients during disease quiescence, suggesting that microbial dysbiosis in IBD may be an underlying disorder independent of disease activity. Microbial modules thus provide an integrative view of microbial ecology relevant to IBD.

| S-EPMC3834335 | biostudies-literature

Risk Factors for Developing Inflammatory Bowel Disease Within and Across Families with a Family History of IBD.

Project description:IntroductionA family history of inflammatory bowel disease [IBD] is the strongest risk factor for disease. However, some first-degree relatives (FDRs) will develop disease, while others will not.MethodsUsing the nationwide Danish National Patient Register, we examined risk factors in families with two or more affected FDRs. First, we compared exposures between siblings with and without IBD within the same family [within-family analysis]. Second, we compared exposures between individuals with and without IBD across all families [across-family analysis]. Exposures included sex, birth order, mode of delivery, antibiotics, personal and family history of immune-mediated diseases, gastrointestinal infections, and surgical history preceding diagnosis. Uni- and multivariable conditional logistic regression analyses were conducted.ResultsIn the 'within-family analysis', 1669 families were included [1732 cases, 2447 controls]. Female sex (adjusted odds ratio [aOR]: 1.40, 95% confidence interval [CI] 1.23, 1.59), history of ankylosing spondylitis [aOR: 2.88, 95% CI 1.05, 7.91] and exposure to antibiotics [aOR: 1.28, 95% CI 1.02, 1.61] increased the risk for IBD. In the 'across-family analysis', 1254 cases and 37 584 controls were included, confirming an association with prior ankylosing spondylitis [aOR: 3.92, 95% CI 1.38, 11.12] and exposure to antibiotics [aOR: 1.29, 95% CI 1.04, 1.60]. Having two or more relatives [aOR: 6.26, 95% CI 1.34, 29.29] or a sibling with IBD [aOR: 1.36, 95% CI 1.18, 1.57] increased the risk of IBD. Appendectomy reduced the risk of ulcerative colitis [aOR: 0.32, 95% CI 0.14, 0.72].ConclusionIn families with IBD, we identified risk factors for the unaffected FDR to develop disease. These findings provide an opportunity for counselling IBD relatives.

| S-EPMC10410093 | biostudies-literature

On the Factors Governing Austenite Stability: Intrinsic versus Extrinsic.

Project description:In this review, we separate the different governing factors on austenite stability into intrinsic and extrinsic factors, depending on the domain defined by austenite grain boundaries. The different measuring techniques on the effectiveness of the governing factors in affecting the austenite stability are discussed. On the basis of the austenite stability, a new alloy design strategy that involves the competition between the intrinsic and extrinsic factors to control the transformation-induced plasticity (TRIP) effect to realize the stronger the more ductile steel is proposed. The present review may provide new insights into the development of novel thermal-mechanical processing to advance the mechanical properties of steels for industrial applications.

| S-EPMC7435654 | biostudies-literature

Characterization of the intestinal mucosal proteome in cats with inflammatory bowel disease and alimentary small cell lymphoma.

Project description:BackgroundCurrent tests for diagnosis and differentiation of lymphoplasmacytic enteritis (LPE) and small cell lymphoma (SCL) in cats are expensive, invasive, and lack specificity. The identification of less invasive, more reliable biomarkers would facilitate diagnosis.ObjectivesTo characterize the mucosal proteome in endoscopically obtained, small intestinal tissue biopsy specimens. We hypothesized that differentially expressed proteins could be identified and serve as biomarker candidates for the differentiation of LPE and SCL in cats.AnimalsSix healthy control cats, 6 cats with LPE, and 8 cats with SCL.MethodsThe mucosal proteome was analyzed using 2-dimensional fluorescence difference gel electrophoresis (2D DIGE) and nanoflow liquid chromatography tandem mass spectrometry. For 5 proteins, results were verified by Western blot analysis.ResultsA total of 2349 spots were identified, of which 9 were differentially expressed with a ≥2-fold change between healthy cats and cats with LPE and SCL (.01 < P < .001). Eight of these 9 spots were also differentially expressed between cats with LPE and cats with SCL (P .001 < P < .04). However, Western blot analysis for malate dehydrogenase-1, malate dehydrogenase-2, apolipoprotein, annexin IV, and annexin V did not confirm significant differential protein expression for any of the 5 proteins assessed.Conclusions and clinical importanceTwo-D DIGE did not identify potential biomarker candidates in the intestinal mucosa of cats with LPE and SCL. Future studies should focus on different techniques to identify biomarker candidates for cats with chronic enteropathies (CE).

| S-EPMC7848303 | biostudies-literature

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