Simon P. Dunlop

Abnormal Intestinal Permeability in Subgroups of Diarrhea-Predominant Irritable Bowel Syndromes

OBJECTIVES:Irritable bowel syndrome (IBS) is a heterogeneous condition and defined according to symptoms. Low-grade inflammation has been associated with IBS, particularly that following infection, but whether altered intestinal permeability profiles relate to irritable bowel subtype or onset is uncertain. Our aim was to compare small and large intestinal permeability in various subtypes of IBS to healthy controls.METHODS:Intestinal permeability was measured using 1.8 MBq of 51Cr-EDTA and collecting urine over 24 h; Study 1: patients with diarrhea-predominant postinfectious IBS (N = 15), constipation-predominant IBS (N = 15), and healthy controls (N = 15); Study 2: two groups of diarrhea-predominant IBS (D-IBS), one with a history of onset after acute gastroenteritis (postinfectious) (N = 15) and the other without such a history (nonpostinfectious) (N = 15) both compared with healthy controls (N = 12).RESULTS:Permeability expressed as percentage of total dose excreted in urine (median [inter-quartile range]). Study 1: Proximal small intestinal permeability was increased in postinfectious IBS (0.19 [0.12–0.23]) in contrast to constipated IBS (0.085 [0.043–0.13]) and controls (0.07 [0.035–0.19]) (p = 0.02). IBS patients with eczema, asthma, or hayfever had increased proximal small intestinal permeability compared with IBS patients without atopy (p = 0.02). Study 2: Small intestinal permeability was greater in nonpostinfectious diarrhea-predominant IBS (0.84 [0.69–1.49]) compared with postinfectious IBS (0.43 [0.29–0.63], p = 0.028) or controls (0.27 [0.2–0.39]), p = 0.001).CONCLUSIONS:Small intestinal permeability is frequently abnormal in diarrhea-predominant IBS. Those without a history of infectious onset appear to have a more severe defect.

Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome

BACKGROUND & AIMS 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists improve symptoms in patients with diarrhea-predominant irritable bowel syndrome (D-IBS), 5-HT 4 agonists help those with constipation-predominant IBS (C-IBS). These data suggest excess or deficiency in 5-HT in D-IBS or C-IBS, respectively. Mucosal 5-HT-containing enterochromaffin cells (EC) are increased in postinfectious IBS (PI-IBS). Our aim was to define the postprandial release of 5-HT in PI-IBS and C-IBS patients and to relate this to mucosal 5-HT turnover. METHODS Fifteen PI-IBS patients with diarrhea-predominant symptoms, 15 C-IBS patients, and 15 healthy controls underwent serial (platelet-poor) plasma 5-HT measurement for 3 hours after a standard 520-kcal meal. Rectal biopsy specimens were assayed for 5-HT and its metabolite 5-hydroxindoleacetic acid (5-HIAA). Colonic transit was measured using radio-opaque markers. RESULTS Colonic transit was prolonged in C-IBS patients (mean +/- SEM) (49.4 +/- 3.8 h) compared with PI-IBS (26.7 +/- 4.5) and control patients (34.1 +/- 4.5) ( P < .02). Release of 5-HT assessed by area under the curve (AUC) of platelet-poor plasma 5-HT from 0 to 180 minutes postprandially was significantly lower in C-IBS patients (2593 +/- 309 mmol/L . min) compared with P-IBS (5623 +/- 721) and control patients (4822 +/- 598) ( P < .001). PI-IBS patients showed significantly higher peak postprandial plasma 5-HT values (median, range) (71.7, 43.4-125.3) ng/L compared with C-IBS patients (31.2, 15.2-40.5) and control patients (43.6, 26.7-50.1) ( P < .01). Mucosal 5-HT turnover as assessed by mucosal 5-HIAA/5-HT ratio was decreased in both C-IBS and PI-IBS patients, .14 (.01-.6) and .21 (.02-2.5), respectively, compared with control patients 1.12 (.17-3.1) ( P < .002). CONCLUSIONS C-IBS patients show impaired postprandial 5-HT release whereas PI-IBS patients have higher peak levels, abnormalities that may be related to their different symptoms.

Randomized, double-blind, placebo-controlled trial of prednisolone in post-infectious irritable bowel syndrome

Background : Post‐infectious irritable bowel syndrome is associated with increased serotonin‐containing enterochromaffin cells and lymphocytes in rectal biopsies. Animal studies have suggested that steroids reduce the lymphocyte response and suppress some of the post‐infectious changes in neuromuscular function.

Age-related decline in rectal mucosal lymphocytes and mast cells.

Background Previous studies have shown that irritable bowel syndrome declines with age and is more common in women. Recent reports suggest that some diarrhoea predominant irritable bowel syndrome patients have low-grade inflammation with increased numbers of mucosal T lymphocytes, 5-hydroxytryptamine (5-HT) containing enteroendocrine cells and mast cells. Objective To determine whether there are age or gender-related changes in mucosal T lymphocytes, mast cells or enteroendocrine cells which might explain these findings. Methods Forty healthy volunteers (20 subjects below 55 years of age and 20 above 55 years) free from gastro-intestinal symptoms or disease answered detailed bowel symptom questionnaires and underwent sigmoidoscopy, rectal biopsy and colonic transit measurement. Biopsies were immunostained and quantified for lamina propria and intra-epithelial T lymphocytes, mast cells and 5-HT and peptide YY enteroendocrine cells. Results There was a reduction in lamina propria T lymphocyte counts (P = 0.018), crypt intra-epithelial T lymphocytes (P = 0.014) and mast cells (P = 0.02) in the > 55 year group. Enteroendocrine cell numbers did not decline with age and were not related to colonic transit. There were no gender differences between any of the cells quantified. Conclusions Lymphocyte and mast cell numbers decline with age in normal large bowel mucosa. Reduced numbers of mucosal inflammatory cells may influence the low-grade inflammatory response to luminal antigens and contribute to the reduction of irritable bowel syndrome observed in older subjects.

Achalasia presenting as acute stridor

We report a case of achalasia presenting as acute stridor and respiratory distress in an 87-year-old woman. A mega-oesophagus was decompressed by aspiration through a naso-oesophageal tube, stiffened with paediatric endoscopic biopsy forceps before placement. Subsequent barium swallow showed mega-oesophagus secondary to achalasia causing tracheal compression at the level of the thoracic inlet. There have been 28 previous case reports of mega-oesophagus due to achalasia causing tracheal obstruction and the literature is reviewed. Recognition and urgent treatment of this very rare complication of achalasia by naso-oesophageal decompression may avoid fatality.

Nutritional issues in irritable bowel syndrome.

Food products have variously been reported as causing, perpetuating or treating irritable bowel syndrome. The evidence for this is reviewed with regard to recent studies investigating symptom reporting, mono- and disaccharide malabsorption and probiotics. The development of objective measures remains an urgent priority because of the high placebo response to any dietary intervention in irritable bowel syndrome.