Faculty Collaboration Database

Alterations in mucosal immunity identified in the colon of patients with irritable bowel syndrome. Clin Gastroenterol Hepatol 2008 Feb;6(2):194-205

Date

02/02/2008

Pubmed ID

18237869

Pubmed Central ID

PMC2453689

DOI

10.1016/j.cgh.2007.11.012

Scopus ID

2-s2.0-38649131433 (requires institutional sign-in at Scopus site)   114 Citations

Abstract

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) has been associated with mucosal dysfunction, mild inflammation, and altered colonic bacteria. We used microarray expression profiling of sigmoid colon mucosa to assess whether there are stably expressed sets of genes that suggest there are objective molecular biomarkers associated with IBS.

METHODS: Gene expression profiling was performed using Human Genome U133 Plus 2.0 (Affymetrix) GeneChips with RNA from sigmoid colon mucosal biopsy specimens from 36 IBS patients and 25 healthy control subjects. Real-time quantitative polymerase chain reaction was used to confirm the data in 12 genes of interest. Statistical methods for microarray data were applied to search for differentially expressed genes, and to assess the stability of molecular signatures in IBS patients.

RESULTS: Mucosal gene expression profiles were consistent across different sites within the sigmoid colon and were stable on repeat biopsy over approximately 3 months. Differentially expressed genes suggest functional alterations of several components of the host mucosal immune response to microbial pathogens. The most strikingly increased expression involved a yet uncharacterized gene, DKFZP564O0823. Identified specific genes suggest the hypothesis that molecular signatures may enable distinction of a subset of IBS patients from healthy controls. By using 75% of the biopsy specimens as a validation set to develop a gene profile, the test set (25%) was predicted correctly with approximately 70% accuracy.

CONCLUSIONS: Mucosal gene expression analysis shows there are relatively stable alterations in colonic mucosal immunity in IBS. These molecular alterations provide the basis to test the hypothesis that objective biomarkers may be identified in IBS and enhance understanding of the disease.

Author List

Aerssens J, Camilleri M, Talloen W, Thielemans L, Göhlmann HW, Van Den Wyngaert I, Thielemans T, De Hoogt R, Andrews CN, Bharucha AE, Carlson PJ, Busciglio I, Burton DD, Smyrk T, Urrutia R, Coulie B

Author

Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Colon
Female
Gene Expression Profiling
Gene Expression Regulation
Humans
Immunity, Mucosal
Intestinal Mucosa
Irritable Bowel Syndrome
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
RNA
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction