Abnormalities of serotonin metabolism and their relation to symptoms in untreated celiac disease.
OBJECTIVE
Serotonin (5-hydroxytryptamine [5-HT]) is a key modulator of gut function that in excess causes nausea, vomiting, and diarrhea. We recently showed that patients with post-infective irritable bowel syndrome have increased postprandial release of 5-HT associated with low-grade T-cell mediated inflammation. Celiac disease is another common disease in which a T-cell enteropathy is associated with increased mucosal 5-HT levels. Our aim was to determine how this inflammatory lesion influenced 5-HT bioavailability and how changes in 5-HT related to the symptoms of nausea, vomiting, and diarrhea seen in untreated celiac patients.


METHODS
Fasting plasma and platelet 5-HT and postprandial plasma 5-HT levels were measured after a high-carbohydrate meal in celiac patients (n = 18) and healthy controls (n = 18) using high-pressure liquid chromatography. Dyspepsia was assessed during the postprandial period using a questionnaire. Finally, we compared the histology and mucosal 5-HT levels in duodenal biopsy specimens from celiac patients and controls.


RESULTS
Celiac patients had increased 5-HT-containing enterochromaffin cell numbers and significantly higher peak plasma 5-HT levels (P = .0002), postprandial area under the curve (P = .0006), and platelet 5-HT stores (P = .031) than controls. Peak 5-HT levels correlated significantly with postprandial dyspepsia scores (P = .005). Celiac patients had higher duodenal 5-HT levels (P = .007) than controls.


CONCLUSIONS
Celiac disease is associated with increased mucosal 5-HT content and enhanced 5-HT release from the upper small bowel, which correlates with postprandial dyspepsia. Serotonin excess may mediate dyspeptic symptoms in untreated celiac disease.
Coleman
Nicholas S
NS
Division of Gastroenterology, School of Medical and Surgical Sciences, University Hospital, Nottingham, United Kingdom.
Foley
Stephen
S
Dunlop
Simon P
SP
Wheatcroft
Johanna
J
Blackshaw
Elaine
E
Perkins
Alan C
AC
Singh
Gulzar
G
Marsden
Charles A
CA
Holmes
Geoffrey K
GK
Spiller
Robin C
RC
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002446:Celiac Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004386:Duodenum / Q000378:metabolism / Q000473:pathology; D004415:Dyspepsia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid