Abnormalities of Serotonin Metabolism and Their Relation to Symptoms in Untreated Celiac Disease

Background & Aims: 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 postinfective 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.