Background: Inflammatory bowel disease (IBD) is a chronic idiopathic gastrointestinal disease. Increasing evidence suggests that microRNAs (miRNAs) may participate in the pathophysiology of IBD.

Methods: A miRCURY™ LNA Array and in situ hybridization were employed to screen for differentially expressed miRNAs (DEMs) in fecal specimens from 41 IBD patients (22 ulcerative colitis (UC), 19 Crohn’s disease (CD)) and 23 healthy controls (HC). RT-qPCR was performed to confirm the findings. The DEMs target genes and corresponding biological functions were predicted by bioinformatics analysis.

Results: Compared with HC, miR-16-5p in the feces was up-regulated both in UC and CD patients (p < 0.01), while miR-21-5p was up-regulated only in UC patients (p < 0.01). TargetScan 7.2, miRWalk, and miRDB were used to predict 216 public target genes of miR-16-5p and miR-21-5p, and six hub genes (PIK3R1, GRB2, SUZ12, NTRK2, Smurf2, and WWP1) were analyzed using the STRING database and Cytoscape. All the hub genes promote the occurrence and development of IBD-related colorectal cancer.

Conclusions: The elevated levels of miR-16-5p and miR-21-5p in feces of IBD patients have to guide significance for the noninvasive clinical diagnosis of IBD and have a warning effect on the occurrence of IBD-related colorectal cancer.