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* = Presenting author

P131 Fecal micro-RNAs indicate disease activity in ulcerative colitis

Verdier J.1, Breunig I.1, Ohse M.C.1, Roy S.1, Groner S.1, Roubrocks S.1, Streetz K.2, Trautwein C.1, Roderburg C.1, Sellge G.*1

1University Hospital RWTH Aachen, Dep. of Internal Medicine III, Aachen, Germany 2Gemeinschaftsklinikum Mittelrhein - Kemperhof, Dep. of Gastroenterology, Kobelnz, Germany

Background

micro-RNAs (miRNAs) are promising biomarkers for personalised medicine owing to their tightly regulated expression and their stability in extracellular environments, suitable with non-invasive sampling methods. In this study, we investigated the expression of fecal miRNAs in Crohn's disease (CD), ulcerative colitis (UC) and Clostridium difficile infection (CDI).

Methods

A Nanostring screen for 800 different human miRNAs was applied to stool samples from 6 controls and 6 active CD patients. Levels of selected miRNAs were further measured by RT-qPCR in stool samples from 24 controls, 23 CD, 24 UC, and 8 CDI patients; in intestinal biopsies from 10 controls, 18 CD, and 23 UC patients; and in serum samples from 29 controls, 30 CD and 20 UC patients.

Results

97 different miRNAs were detected in fecal samples, with miR-1246 being the most prominent miRNA in both controls and patients. A distinct fecal miRNA profile, with higher levels of miR-223 and miR-1246, was observed in the most active CD patients with colonic involvement. RT-qPCR indicates that expression levels of these two miRNA are mostly elevated in UC patients while levels of fecal miR-1246, but not miR-223, are higher in CDI patients. In UC patients, fecal miR-223 and miR-1246 levels correlate with fecal Calprotectin (rs =0.61 and 0.51, p<0.001) and CRP (rs =0.56 and 0.46, p<0.001). Fecal miR-223 and miR-1246 levels very efficiently differentiate between endoscopically inactive (endoscopic Mayo Score 0/1) versus active disease (endoscopic Mayo Score 2/3). ROC curve analysis show the following area under the curve (AUC) results: Calprotectin 0.95, p<0.001; miR223 0.92, p<0.001; CRP 0.88, p<0.01; miR-1246 AUC 0.87, p<0.01; SCCAI 0.83; p<0.01). In biopsies, only miR-223 expression is increased in UC patients and serum levels of miR-223 and miR-1246 are not different between controls and patients.

Conclusion

Fecal miR-223 and miR-1246 are markers of active UC and fecal miR-223 has the potential to differentiate between active UC and CDI.