Abnormal small-intestinal endocrine cells in patients with irritable bowel syndrome.

BACKGROUND: General disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). The gastrointestinal tract hormones play an important role in regulating gastrointestinal motility. AIMS: To investigate a possible abnormality in the small intestinal endocrine cells of IBS patients. METHODS: Included in the study were 41 patients with irritable bowel syndrome according to Rome Criteria III and 42 healthy controls. Duodenal biopsies were obtained from both patients and controls during gastroscopy. The biopsies were immunostained by avidin-biotin-complex method for secretin, CCK, GIP, somatostatin, and serotonin cells. The cell densities were quantified by computerized image analysis. RESULTS: The density of secretin- and CCK-immunoreactive cells in patients with IBS was significantly reduced. The reduction in secretin and CCK cells occurred only in IBS-diarrhea patients, but not in IBS-constipation subtype. Both GIP and somatostatin cell densities were reduced in the duodenum of IBS patients. There was no statistical difference between the subtypes of IBS patients, regarding secretin, CCK, GIP, or somatostatin cell densities. Serotonin cell density was not affected in patients with IBS. CONCLUSIONS: The low densities of secretin and CCK cells in IBS-diarrhea patients may cause a functional pancreatic insufficiency as well as inadequate gall emptying, as these hormones stimulate pancreatic bicarbonate and enzyme secretion and CCK stimulates as well gall bladder contraction. Low densities of secretin, GIP, and somatostatin cells in IBS patients might result in a high secretion of gastric acid, as secretin, GIP, and somatostatin inhibit gastric acid secretion.

Relative importance of abnormalities of CCK and 5-HT (serotonin) in Giardia-induced post-infectious irritable bowel syndrome and functional dyspepsia.

BACKGROUND: Post-infectious irritable bowel syndrome (PI-IBS) and functional dyspepsia (FD) have been described after both Campylobacter jejuni gastroenteritis and Giardia infection. After C. jejuni, there is increased rectal serotonin (5-HT)-containing EC cells and postprandial plasma 5-HT, while a pilot study suggested increased plasma cholecystokinin (CCK) after Giardia infection. AIM: To determine changes in plasma and duodenal mucosal 5-HT and CCK in Giardia-induced PI-IBS. METHODS: A total of 32 patients previously infected with Giardia and 19 who had recovered fully (controls) completed symptom questionnaires. Endoscopic duodenal biopsies were obtained from all subjects and immunohistochemically stained for CCK, 5-HT and CgA containing entero-endocrine cells and mast cells. 5-HT content was also assessed. Twenty-one of 32 patients and 19 controls consumed a high-carbohydrate meal, while fasting and postprandial plasma CCK and 5-HIAA were measured. RESULTS: Post-infectious irritable bowel syndrome patients had increased numbers of CCK cells (P = 0.02), but lower numbers of EC cells (P = 0.009). Plasma CCK did not differ significantly between the groups, but correlated significantly with postprandial dyspepsia scores (r = 0.5, P = 0.05). PI-IBS patients had significantly lower plasma 5-HIAA, before and after meal (P = 0.05) as well as more dyspepsia (P < 0.0001) compared with recovered subjects. CONCLUSIONS: Post-infectious bowel dysfunction following Giardia infection is associated with increased duodenal mucosal CCK. Postprandial dyspeptic symptoms correlate better with CCK than measures of 5-HT metabolism.

Increased visceral sensitivity in Giardia-induced postinfectious irritable bowel syndrome and functional dyspepsia. Effect of the 5HT3-antagonist ondansetron.

In an outbreak of waterborne giardiasis where 1300 subjects were diagnosed, with Giardia lamblia, 139 continued to have abdominal symptoms of whom two of three had negative stool culture and microscopy. These were considered to have a postinfectious functional gastrointestinal disorder. We investigated visceral hypersensitivity in patients with persisting abdominal symptoms after Giardia infection and assessed the effect of 5HT(3)-antagonist ondansetron. Twenty-two patients with Giardia negative stools and 19 controls were included. A subset of patients (n = 15) had both irritable bowel syndrome (IBS) and functional dyspepsia (FD). All subjects underwent a satiety test with a soup combined with three-dimensional ultrasound. Fifteen of 22 patients underwent double-blind, randomized, placebo-controlled study with the 5-HT(3) antagonist ondansetron given orally. Drinking capacity was lower in patients than in controls (P < 0.01) and gastric emptying was reduced (P < 0.05). Patients had more symptoms both fasting and postprandially (P < 0.001) compared to controls. Ondansetron had no effect on these parameters except from less nausea postprandially (P < 0.05). In conclusion, patients with Giardia-induced gastrointestinal symptoms developed both IBS and FD. They exhibited gastric hypersensitivity with lower drinking capacity and delayed gastric emptying. The 5-HT(3) antagonist ondansetron did not improve drinking capacity, gastric emptying or symptoms except nausea.