Transcriptional Signatures That Define Ulcerative Colitis in Remission

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 0-glycosylation (MUCI7, MUC3A, MUCSAC, MUCI2, SPONI, B3GNT3), ephrin-mediated repulsion of cells (EFNB2E, EFNA3, EPHAIO, EPHAI), GAP junction trafficking (TUBAI C, TUBA4A, TUBB4B, GJB3, CLTB), and decreased expression of several toll-like receptors (TLRI, 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.

Automated summary

This study used RNA-Seq technology to compare remission, active UC, and healthy control patients, identifying specific transcriptional signatures for UC in remission with changes in gene expression levels. The results showed partial restoration and improvement of homeostasis in the epithelial mucus layer and revival of immunological functions in UC remission patients. The composition of bacterial gut flora may play a key role in UC remission.