Faecal Micro-RNAs in Inflammatory Bowel Diseases

Abstract

Background and Aims Faecal biomarkers are used as indicators of disease activity in inflammatory bowel diseases [IBD], which include Crohn’s disease [CD] and ulcerative colitis [UC]. Micro-RNAs [miRNAs] are small non-coding RNAs detectable in extracellular fluids and can be used as clinical biomarkers. The aim of this study was to determine if faecal miRNA composition is altered in IBD. Methods More than 800 different human faecal miRNAs were measured in stool samples from control individuals and patients with active CD by using NanoString technology. Selected miRNAs were quantified by qRT-PCR in faeces, serum and intestinal tissue of controls [n = 23] and patients with inactive or active CD [n = 22, n = 22] or UC [n = 11, n = 24] as well as patients with Clostridium difficile infection [CDI, n = 8]. Results In total, 150 miRNAs were significantly detected in faeces from controls and patients, and multivariate analyses showed that CD patients with high disease activities had a distinct miRNA profile and that miR-223 and miR-1246 were distinct from other faecal miRNAs. In a larger cohort, active UC patients displayed significantly higher levels of miR-223 and miR-1246 than controls while patients with CDI had higher levels of faecal miR-1246 but not miR-223. No differences were noted in serum samples. Conclusions To our knowledge, this is the first comprehensive screen of faecal miRNAs performed in IBD. Further investigation will aim to confirm these findings in a larger cohort and to understand the biological function and cellular sources of faecal miRNAs.

Biomarkers of Inflammation in Inflammatory Bowel Disease: How Long before Abandoning Single-Marker Approaches?

“…These markers are very attractive because of their stability in the extracellular environment and the ease and specificity at which they can be detected. Data in IBD are starting to accumulate, with identification of several miRNAs in the whole blood [82], serum [83][84][85], faeces [85,86], and in-DOI: 10.1159/000511641 testinal tissues [83,[87][88][89] of patients with active IBD that differ from those in patients with quiescent disease and controls. Interestingly, miRNAs have been suggested as potential predictors of response to therapy since levels of let-7d and let-7e were significantly elevated at week 6 of the IFX induction regimen in patients achieving clinical remission [90].…”

“…Recently, >800 faecal miRNAs have been investigated in stool samples of patients with both UC and CD and compared to controls [86]. Findings suggest that patients with active CD and UC have distinct faecal miRNA profiles compared to non-IBD patients, particularly higher levels of miRNA-223 and miRNA-1246 [86].…”

A Prospective Cohort Study of Fecal miR-223 and miR-451a as Noninvasive and Specific Biomarkers for Diagnosis of Necrotizing Enterocolitis in Preterm Infants

“…miR-223 has been reported to be one of the important mediators in the pathogenesis of inflammatory bowel disease (IBD) [17] and highly expressed in serum and fecal samples of these patients [18, 19]. Wang et al [20] suggested that miR-223 directly targeted Claudin 8 ( CLDN8 ) and interacted with the IL-23 pathway which resulted in interference of the intestinal barrier function in IBD rodent models.…”

“…Due to their biochemical stability in the fecal medium [25, 26], these miRNAs should theoretically be good candidates for noninvasive diagnosis of inflammatory GI conditions. Recently, this concept has been validated successfully in screening programs for colorectal cancer [27] and IBD [19].…”

Fecal MicroRNAs as Potential Biomarkers for Screening and Diagnosis of Intestinal Diseases

“…Dysregulation of miRNA expression in intestine is related to different disease and provides the information to define new miRNA biomarkers; for example, the altered expression profile of fecal miRNA composition in active IBD patients versus control has been identified and fecal miR-223 and miR-1246 are found upregulated in the stool of active IBD patients ( Verdier et al, 2019 ). Another study identified the highest expression of miR-21, miR-155, and miR-223 in feces of IBD patients and overexpression of miR-21 has been shown to cause intestinal epithelial barrier impairment.…”