Brief Article
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World J Gastroenterol. Mar 7, 2014; 20(9): 2383-2391
Published online Mar 7, 2014. doi: 10.3748/wjg.v20.i9.2383
Endocrine cells in the ileum of patients with irritable bowel syndrome
Magdy El-Salhy, Odd Helge Gilja, Doris Gundersen, Jan Gunnar Hatlebakk, Trygve Hausken
Magdy El-Salhy, Section for Gastroenterology, Department of Medicine, Stord Helse-Fonna Hospital, 54 09 Stord, Norway
Doris Gundersen, Department of Research, Helse-Fonna, 55 01 Haugesund, Norway
Magdy El-Salhy, Odd Helge Gilja, Jan Gunnar Hatlebakk, Trygve Hausken, Section for Gastroenterology, Department of Clinical Medicine, University of Bergen, 50 00 Bergen, Norway
Author contributions: El-Salhy M designed the study, performed research, analyzed the results, and wrote the manuscript; Gilja OH, Gundersen D, Hatlebakk JG and Hausken T contributed equally to the study design, analysis of the results, and commenting upon the manuscript; All the authors approved the submitted version of the manuscript.
Supported by A Grant from Helse-Fonna
Correspondence to: Magdy El-Salhy, Professor, Consultant Gastroenterologist, Section for Gastroenterology, Department of Medicine, Stord Helse-Fonna Hospital, Box 4000, 54 09 Stord, Norway. magdy.el-salhy@helse-fonna.no
Telephone: +47-53-491000 Fax: +47-53-491001
Received: September 10, 2013
Revised: October 20, 2013
Accepted: November 18, 2013
Published online: March 7, 2014
Processing time: 177 Days and 10.1 Hours
Abstract

AIM: To study the ileal endocrine cell types in irritable bowel syndrome (IBS) patients.

METHODS: Ninety-eight patients with IBS (77 females and 21 males; mean age 35 years, range 18-66 years) were included, of which 35 patients had diarrhea (IBS-D), 31 patients had a mixture of both diarrhea and constipation (IBS-M), and 32 patients had constipation (IBS-C) as the predominant symptoms. The controls were 38 subjects (26 females and 12 males; mean age 40 years, range 18-65 years) who had submitted to colonoscopy for the following reasons: gastrointestinal bleeding, where the source of bleeding was identified as hemorrhoids (n = 24) or angiodysplasia (n = 3), and health worries resulting from a relative being diagnosed with colon carcinoma (n = 11). The patients were asked to complete the: Birmingham IBS symptom questionnaire. Ileal biopsy specimens from all subjects were immunostained using the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), enteroglucagon, and somatostatin cells. The cell densities were quantified by computerized image analysis, using Olympus cellSens imaging software.

RESULTS: The gender and age distributions did not differ significantly between the patients and the controls (P = 0.27 and P = 0.18, respectively). The total score of Birmingham IBS symptom questionnaire was 21 ± 0.8, and the three underlying dimensions: pain, diarrhea, and constipation were 7.2 ± 0.4, 6.6 ± 0.4, and 7.2 ± 0.4, respectively. The density of serotonin cells in the ileum was 40.6 ± 3.6 cells/mm2 in the controls, and 11.5 ± 1.2, 10.7 ± 5.6, 10.0 ± 1.9, and 13.9 ± 1.4 cells/mm2 in the all IBS patients (IBS-total), IBS-D, IBS-M, and IBS-C patients, respectively. The density in the controls differed significantly from those in the IBS-total, IBS-D, IBS-M, and IBS-C groups (P < 0.0001, P = 0.0001, P = 0.0001, and P < 0.0001, respectively). There was a significant inverse correlation between the serotonin cell density and the pain dimension of Birmingham IBS symptom questionnaire (r = -0.6, P = 0.0002). The density of PYY cells was 26.7 ± 1.6 cells/mm2 in the controls, and 33.1 ± 1.4, 27.5 ± 1.4, 34.1 ± 2.5, and 41.7 ± 3.1 cells/mm2 in the IBS-total, IBS-D, IBS-M, and IBS-C patients, respectively. This density differed significantly between patients with IBS-total and IBS-C and the controls (P = 0.03 and < 0.0001, respectively), but not between controls and, IBS-D, and IBS-M patients (P = 0.8, and P = 0.1, respectively). The density of PYY cells correlated significantly with the degree of constipation as recorded by the Birmingham IBS symptom questionnaire (r = 0.6, P = 0.0002). There were few PP-, enteroglucagon-, and somatostatin-immunoreactive cells in the biopsy material examined, which made it impossible to reliably quantify these cells.

CONCLUSION: The decrease of ileal serotonin cells is associated with the visceral hypersensitivity seen in all IBS subtypes. The increased density of PYY cells in IBS-C might contribute to the constipation experienced by these patients.

Keywords: Computer image analysis; Irritable bowel syndrome; Ileum; Peptide YY; Serotonin

Core tip: The present study investigated for the first time the ileal endocrine cells in patients with irritable bowel syndrome (IBS). It included a relatively a large cohort of patients and comprising all the IBS subtypes, namely diarrhea (IBS-D), a mixture of both diarrhea and constipation (IBS-M) and constipation (IBS-C). It showed that the density of serotonin cells is reduced in patients with IBS, regardless of the subtype. On the other hand the density of peptide YY (PYY) cells in the ileum of IBS-D and IBS-M patients did not differ from that of controls, but was significantly elevated in those with IBS-C. It was concluded that the reduction of ileal serotonin cells may be connected to the visceral hypersensitivity seen in all IBS subtypes and that increase in the PYY cell density in IBS-C, would slow the intestinal transit and cause constipation.