Sigmoid colon mucosal gene expression supports alterations of neuronal signaling in irritable bowel syndrome with constipation

Objective: Peripheral factors likely play a role in at least a subset of irritable bowel syndrome (IBS) patients. Few studies have investigated mucosal gene expression using an unbiased approach. Here, we performed mucosal gene profiling in a sex-balanced sample to identify relevant signaling pathways and gene networks and compare to publicly available profiling data from additional cohorts. Design: 20 Rome III+ IBS patients (10 IBS with constipation (IBS-C), 10 IBS with diarrhea (IBS-D) 5 men/women each) and 10 age/sex-matched healthy controls (HCs) underwent sigmoidoscopy with biopsy for gene microarray analysis, including differential expression, weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis and comparison with publicly available data. Expression levels of 67 genes were validated in an expanded cohort, including the above samples and 18 additional participants (6 each IBS-C, IBS-D, HCs) using the NanoString nCounter technology. Results: There were 1270 differentiall...