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. 2010 Jul;139(1):249-58.
doi: 10.1053/j.gastro.2010.03.032. Epub 2010 Mar 17.

Serotonin signaling is altered in irritable bowel syndrome with diarrhea but not in functional dyspepsia in pediatric age patients

Christophe Faure  1 , Natalie Patey, Cindy Gauthier, Elice M Brooks, Gary M Mawe
Affiliations

Serotonin signaling is altered in irritable bowel syndrome with diarrhea but not in functional dyspepsia in pediatric age patients

Christophe Faure et al. Gastroenterology. 2010 Jul.

Abstract

Background & aims: In adults, irritable bowel syndrome (IBS) and functional dyspepsia (FD) are chronic conditions that often start during childhood. We investigated mucosal serotonin (5-HT) signaling in children with the idea that data from subjects with a shorter history may improve our understanding of underlying pathophysiological mechanisms.

Methods: Ninety-eight children undergoing gastroscopy or colonoscopy were studied prospectively. Biopsy specimens were evaluated for inflammation, enterochromaffin cell numbers, 5-HT content, and messenger RNA (mRNA) levels for the synthetic enzyme, tryptophan hydroxylase 1, and the serotonin transporter (SERT) were assessed by quantitative real-time reverse-transcription polymerase chain reaction.

Results: Data from 12 children with IBS and 17 with FD were compared with age-matched controls (12 with rectal biopsies and 12 with gastric biopsies) and with subjects with organic disorders. In patients with FD, a small number of immune cells were observed in the gastric mucosa in half of the patients, but no abnormalities with respect to the 5-HT pathway were identified. In patients with IBS, no differences were detected between patients and controls regarding intraepithelial lymphocytes and CD3+ cells in the lamina propria although all patients showed at least a slight inflammatory infiltrate. In the IBS samples, higher 5-HT content (P < .01) and lower SERT mRNA (P < .05) were detected as compared with controls. Severe inflammation in the colonic mucosa had a high impact on 5-HT signaling with a significant decrease in enterochromaffin cells (P < .01) and 5-HT content (P < .01) and a high SERT mRNA expression (P < .01).

Conclusions: These results confirm the role of 5-HT signaling in IBS in children and argue against such a role in FD.

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Conflict of interest statement

Conflict of interest: NONE

Figures

Figure 1
Figure 1
(A) Enteroendocrine (chromogranin positive) cell and (B) enterochromaffin (5-HT positive) cell counts in the gastric mucosa of patients with functional dyspepsia (FD) are similar as compared to control subjects and subjects with organic diseases. (C) Enteroendocrine (chromogranin positive) cell and (D) enterochromaffin (5-HT positive) cell counts in the rectal mucosa of patients with irritable bowel syndrome (IBS), control subjects and subjects with organic diseases with inflammation grading ≥ 2 (Inflammed organic disorders) and without inflammation (Non-inflammed organic disorders). No significant differences were detected in enteroendocrine and enterochromaffin cell counts of samples from patients with IBS as compared to controls. Biopsies with inflammation grading ≥ 2 obtained from subjects with organic disease exhibited significant lower enteroendocrine and enterochromaffin cell counts as compared to controls and biopsies without inflammation (grade ≤ 1).
Figure 2
Figure 2
(A) Serotonin (5-HT) content in the gastric mucosa of patients with functional dyspepsia (FD) is similar as compared to control subjects and subjects with organic diseases. (B) 5-HT content in the rectal mucosa of patients with irritable bowel syndrome (IBS), control subjects and subjects with organic diseases with inflammation grading ≥ 2 (Inflammed organic disorders) and without inflammation (Non-inflammed organic disorders). 5-HT content is significantly higher in the rectal mucosa of patients with IBS as compared to control subjects. 5-HT levels are significantly lower in biopsies obtained from subjects with Inflammed organic disorders as compared to controls and biopsies from Non-inflammed organic disorders.
Figure 3
Figure 3
Relative expression of tryptophan hydroxylase-1 (TpH-1) mRNA in the rectal mucosa of patients with irritable bowel syndrome (IBS), control subjects and subjects with organic diseases with inflammation grading ≥ 2 (Inflammed organic disorders) and without inflammation (Non-inflammed organic disorders). No significant differences were detected in TpH-1 transcript levels of samples from patients with IBS as compared to controls. TpH-1 transcript levels are significantly higher in biopsies obtained from subjects with Inflammed organic disorders as compared to controls and biopsies from Non-inflammed organic disorders.
Figure 4
Figure 4
Relative expression of serotonin reuptake transporter (SERT) mRNA in the rectal mucosa of patients with irritable bowel syndrome (IBS), control subjects and subjects with organic diseases with inflammation grading ≥ 2 (Inflammed organic disorders) and without inflammation (Non-inflammed organic disorders). A significantly lower level of SERT transcript was detected in samples from patients with IBS as compared to controls. SERT transcript levels are significantly increased in biopsies obtained from subjects with Inflammed organic disorders as compared to controls and biopsies from Non-inflammed organic disorders.
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