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Sigmoid colon mucosal gene expression supports alterations of neuronal signaling in irritable bowel syndrome with constipation.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2018 Jul 01; Vol. 315 (1), pp. G140-G157. Date of Electronic Publication: 2018 Mar 22. - Publication Year :
- 2018
-
Abstract
- 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 with publicly available profiling data from additional cohorts. Twenty 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 coexpression 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 of IBS-C, IBS-D, HCs) using NanoString nCounter technology. There were 1,270 differentially expressed genes (FDR < 0.05) in IBS-C vs. HCs but none in IBS or IBS-D vs. HCs. WGNCA analysis identified activation of the cAMP/protein kinase A signaling pathway. Nine of 67 genes were validated by the NanoString nCounter technology (FDR < 0.05) in the expanded sample. Comparison with publicly available microarray data from the Mayo Clinic and University of Nottingham supports the reproducibility of 17 genes from the microarray analysis and three of nine genes validated by nCounter in IBS-C vs. HCs. This study supports the involvement of peripheral mechanisms in IBS-C, particularly pathways mediating neuronal signaling. NEW & NOTEWORTHY Peripheral factors play a role in the pathophysiology of irritable bowel syndrome (IBS), which, to date, has been mostly evident in IBS with diarrhea. Here, we show that sigmoid colon mucosal gene expression profiles differentiate IBS with constipation from healthy controls. These profiling data and analysis of additional cohorts also support the concept that peripheral neuronal pathways contribute to IBS pathophysiology.
- Subjects :
- Biopsy methods
Female
Genome-Wide Association Study
Humans
Male
Middle Aged
Peripheral Nervous System metabolism
Signal Transduction genetics
Colon, Sigmoid innervation
Colon, Sigmoid metabolism
Colon, Sigmoid pathology
Constipation etiology
Constipation genetics
Constipation physiopathology
Diarrhea etiology
Diarrhea genetics
Diarrhea physiopathology
Gene Expression physiology
Gene Expression Profiling methods
Gene Expression Profiling statistics & numerical data
Intestinal Mucosa metabolism
Intestinal Mucosa pathology
Irritable Bowel Syndrome diagnosis
Irritable Bowel Syndrome genetics
Irritable Bowel Syndrome physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1547
- Volume :
- 315
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 29565640
- Full Text :
- https://doi.org/10.1152/ajpgi.00288.2017