Endocrine cells in the ileum of patients with irritable bowel syndrome

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/mm(2) 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; Ileum; Irritable bowel syndrome; Peptide YY; Serotonin.

Figure 1

Serotonin cell densities in the ileum of controls and in all patients with irritable bowel syndrome, patients with diarrhea as the predominant symptom, patients with both diarrhea and constipation, and patients with constipation as the predominant symptom patients. ^bP < 0.01 vs controls. IBS-total: All patients with irritable bowel syndrome; IBS-D: Patients with diarrhea as the predominant symptom; IBS-M: Patients with both diarrhea and constipation; IBS-C: Patients with constipation as the predominant symptom.

Figure 2

Ileal serotonin-immunoreactive cells in a control subject (A) and a patient with irritable bowel syndrome (B).

Figure 3

Peptide YY cell densities in the ileum of controls and in all patients with irritable bowel syndrome, patients with diarrhea as the predominant symptom, patients with both diarrhea and constipation, and patients with constipation as the predominant symptom patients. ^aP < 0.05, ^bP < 0.01 vs controls. PYY: Peptide YY; IBS-total: All patients with irritable bowel syndrome; IBS-D: Patients with diarrhea as the predominant symptom; IBS-M: Patients with both diarrhea and constipation; IBS-C: Patients with constipation as the predominant symptom.

Figure 4

Peptide YY cells in the ileum of a control subject (A), a patient with irritable bowel syndrome into diarrhea (B), and a patient with irritable bowel syndrome into constipation (C).