Transcriptional Signatures That Define Ulcerative Colitis in Remission

Abstract

Background This study addresses whether existing specific transcriptional profiles can improve and support the current status of the definition of ulcerative colitis (UC) remission apart from the existing endoscopic, histologic, and laboratory scoring systems. For that purpose, a well-stratified UC patient population in remission was compared to active UC and control patients and was investigated by applying the next-generation technology RNA-Seq. Methods Mucosal biopsies from patients in remission (n = 14), patients with active UC (n = 14), and healthy control patientss (n = 16) underwent whole-transcriptome RNA-Seq. Principal component analysis, cell deconvolution methods, gene profile enrichment, and pathway enrichment methods were applied to define a specific transcriptional signature of UC in remission. Results Analyses revealed specific transcriptional signatures for UC in remission with increased expression of genes involved in O-glycosylation (MUC17, MUC3A, MUC5AC, MUC12, SPON1, B3GNT3), ephrin-mediated repulsion of cells (EFNB2E, EFNA3, EPHA10, EPHA1), GAP junction trafficking (TUBA1C, TUBA4A, TUBB4B, GJB3, CLTB), and decreased expression of several toll-like receptors (TLR1, TLR3, TLR5, TLR6). Conclusions This study reveals specific transcriptional signatures for remission. Partial restoration and improvement of homeostasis in the epithelial mucus layer and revival of immunological functions were observed. A clear role for bacterial gut flora composition can be implied. The results can be useful for the development of treatment strategies for UC in remission and may be useful targets for further investigations aiming to predict the outcome of UC in the future.

Impaired Luminal Control of Intestinal Macrophage Maturation in Patients With Ulcerative Colitis During Remission

“…10 In addition, recent gene expression studies have shown the presence of a continuous inflammatory-like state and a gene dysregulation in colonic biopsy specimens from patients with quiescent UC. [11][12][13] The immunomodulating determinants involved in the education of intestinal macrophages still are not fully defined, but intestinal microbiota and microbiota-derived metabolites increasingly are recognized for their role in imprinting tissue-specific features of intestinal macrophages. 5,14 In addition to this, it is known that UC patients show a dysbiotic microbiota composition, including a decrease in Firmicutes and Bacteroidetes phyla 15,16 and altered fecal metabolite profiles, 17 which could affect intestinal macrophage maturation.…”

“… 10 In addition, recent gene expression studies have shown the presence of a continuous inflammatory-like state and a gene dysregulation in colonic biopsy specimens from patients with quiescent UC. 11 , 12 , 13 …”

Dynamic, Transient, and Robust Increase in the Innervation of the Inflamed Mucosa in Inflammatory Bowel Diseases

“…To test whether a similar phenomenon may occur in IBD patients, we investigated IBD transcriptomic datasets. For this, we analyzed two publicly available IBD transcriptomic datasets: (a) the treatment of a naïve pediatric ulcerative colitis cohort (PROTECT [ 32 ]), representing patients from both sexes with active UC as well as control patients without active ulcerative colitis; and (b) a dataset representing adult active UC and UC in remission and controls (Fenton et al cohort) [ 33 ]. Interestingly, consistent with our observations on the experimental colitis, UC patients also showed an increased expression in the genes for neuroglia ( Figure 3 A).…”

“…We used previously published transcriptomic datasets from PROTECT [ 32 ] (accession: GSE109142, 206 samples from ulcerative colitis, and 20 samples from non-inflamed rectum tissues) and Fenton et al [ 33 ] (accession: GSE128682, 16 control samples from normal colon tissues, 14 samples from active ulcerative colitis colon tissues, and 14 samples from colon tissues from ulcerative colitis patients in remission) cohorts. The gene expression changes in the neuroglial identifiers established in our study were evaluated.…”

Transcription Factors That Regulate the Pathogenesis of Ulcerative Colitis

“…Datasets. The gene expression data were collected from the Gene Expression Omnibus (GEO) database with accession GSE128682, and the sample collection was described in an earlier study [14]. The counts for each sample were normalized by DESeq2 [15].…”