The Diagnosis Effect of DNA Methylation in Inflammatory Bowel Diseases

Abstract

We read with great interest the article by Howell et al,1Howell K.J. et al.Gastroenterology. 2018; 154: 585-598Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar who presented the findings of DNA methylation and transcription pattern in intestinal epithelial cells of children with inflammatory bowel disease (IBD). The authors concluded that there are epigenetic and transcriptomic changes within intestinal epithelial cells in patients with IBD. These are impressive findings that raise 3 important issues. First, Howell et al1Howell K.J. et al.Gastroenterology. 2018; 154: 585-598Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar analyzed genome-wild DNA methylation patterns and gene expression of mucosal biopsies collected from children with IBD. The results revealed signature differences in the methylation and gene expression profiles by gut segment. This is a very convincing result, but questions remain. Biopsy is an invasive examination; it is limited owing to trauma, inaccessibility, complications, and ethical problems. Thus, it is necessary to quantify DNA methylation in peripheral blood mononuclear cells from children with IBD. A study has been undertaken to detect DNA methylation in peripheral blood mononuclear cells from 149 patients with IBD (88 Crohn’s disease [CD], 61 ulcerative colitis [UC]).2McDermott E. et al.J Crohns Colitis. 2016; 10: 77-86Crossref PubMed Scopus (94) Google Scholar The result showed that 1443 (97%) of the UC-associated differentially methylated positions (DMPs) also differentially methylated in CD. Of note, 1753 CD DMPs (55%) were differentially methylated in CD only, and 38 UC DMPs (3%) were unique UC-associated DMPs, which imply the presences of a disease-specific alterations in peripheral blood mononuclear cells epigenetic patterns in patients with IBD. Second, should repetitive elements be analyzed of the mucosal biopsies or blood samples? Howell et al have analyzed the genome-wild DNA methylation and successfully detected the DMPs between CD/UC and controls. Previous studies have shown that repetitive elements are often used to represent global methylation changes. Methylation levels of Alu, long interspersed nucleotide elements (LINE-1), and satellite 2 (Sat2) sequences were significantly associated with global 5-methylcytosine content.3Weisenberger D.J. et al.Nucleic Acids Res. 2015; 33: 6823-6836Crossref Scopus (591) Google Scholar In the human genome, there are about half a million LINE1, and almost 1.4 million Alu repetitive elements that contribute to more than one-third of DNA methylation.4Yang A.S. et al.Nucleic Acids Res. 2004; 32: e38Crossref PubMed Scopus (848) Google Scholar Thus, should these data be supplemented so that more information about the methylation patterns of IBD in children could be described? Third, Howell et al used 16S rRNA gene profiling to analysis the adjacent microbiota that were isolated from biopsies, and gut segment and disease-associated changes in microbial composition were detected by supervised analysis. But no significant correlations were identified between DEGs and 16S abundances or dose-dependent relationships for subgroups of patients. In a review, Low et al5Low D. et al.World J Gastroenterol. 2013; 19: 5238-5249Crossref PubMed Scopus (29) Google Scholar have discussed the advancement in methylation of IBD, they found commensal microbes have an ability to alter DNA methylation status. However, most studies were focused on 1 special DNA, such as CXCL16, and also analyzed the possible reason of how bacteria affect the host DNA methylation pattern. Thus, should there be a focus on the relationship between special DMRs and microbiota? Methylation patterns in IBD have been studied for decades, but until now there has been no standardized database of methylated genes in IBD. Thus, more in-depth study of DNA methylation of IBD is needed. DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate With OutcomeGastroenterologyVol. 154Issue 3PreviewWe analyzed DNA methylation patterns and transcriptomes of primary intestinal epithelial cells (IEC) of children newly diagnosed with inflammatory bowel diseases (IBD) to learn more about pathogenesis. Full-Text PDF Open AccessReplyGastroenterologyVol. 155Issue 1PreviewWe would like to thank Baihui Liu, Kuiran Dong, and Rui Dong as well as Ana Savić Mlakar, Iva Hojsak, and Krešo Bendelja for their interest in our article.1 We read their letters with great interest and provide our response herein. Full-Text PDF