Prospective, double-blind diagnostic multicentre study of confocal laser endomicroscopy for wheat sensitivity in patients with irritable bowel syndrome

Abstract

ObjectiveA considerable proportion of patients with irritable bowel syndrome (IBS) may be wheat-sensitive and respond to a gluten-free diet (GFD) although they do not have coeliac disease. However, a diagnostic test for wheat sensitivity (WS) is missing. Our study evaluated the diagnostic accuracy (sensitivity and specificity) of confocal laser endomicroscopy (CLE) for the identification of WS as primary outcome.DesignIn this prospective, double-blind diagnostic study 147 non-coeliac patients fulfilling the Rome III criteria for IBS were tested by CLE for duodenal changes after wheat (index test), soy, yeast or milk exposure. Patients with IBS responding to 2 months of GFD were classified as having WS (reference test) using response criteria recommended by regulatory bodies for pharmaceutical trials of patients with IBS. After 2 months, CLE results were unblinded and patients were advised to exclude those food components that had led to a positive CLE reaction. The clinical response was assessed at follow-up after 6 and 12 months.ResultsOf 130 patients who completed the study per protocol, 74 (56.9%) responded to GFD and were classified as WS after 2 months, and 38 of these 74 patients were correctly identified by CLE (sensitivity 51.4%; 97.5% CI: 38.7% to 63.9%). A total of 38 of 56 patients without WS were correctly identified by CLE (specificity 67.9%; 97.5% CI: 52.9% to 79.9%). At 6 months follow-up, CLE correctly identified 49 of 59 food-sensitive patients (sensitivity 83.1%; 97.5% CI: 69.9% to 91.3%) but specificity was only 32% (97.5% CI: 15.7% to 54.3%).ConclusionIn light of the high proportion of patients with IBS responding to GFD, the diagnostic accuracy of CLE is too low to recommend widespread use of this invasive procedure.Trail registration numberThis study was registered as clinical trial in the German Registry for Clinical Studies (DRKS00010123).

The Role of Food in the Treatment of Bowel Disorders: Focus on Irritable Bowel Syndrome and Functional Constipation

“…Third, specific immune reactions to food antigen exposure might better identify problem foods. Gutspecific reactions have been demonstrated in patients with foodrelated symptoms by the demonstration of IgE and mast cell activation associated with intramucosal injection of food antigens (64) and by the direct observations of injury response using confocal laser endomicroscopy after topical application of specific food antigens to the duodenum and an intramucosal injection of antigens during colonoscopy (67)(68)(69)(70). Both methods have provided evidence that dietary restriction of implicated antigens led to clinical benefits for patients.…”

Probing the leak pathway: Live‐cell imaging of macromolecule passage through epithelia

“…Direct imaging of fluorescent tracers was used to address barrier function in live epithelia and mucosae, but provides limited spatiotemporal resolution as there is little or no retention in target areas/structures. 21,43,44 By using the sandwich assay, an endpoint leak detection assay, previous work in our lab had already suggested that macromolecule passage in epithelia is rather rare across epithelial layers. 23 As a matter of fact, globally assessed permeability does not allow on to safely conclude about the underlying mechanisms since passage can, by way of example, be located to specific subareas of the layer only.…”

Mechanisms Underlying Food-Triggered Symptoms in Disorders of Gut-Brain Interactions

“…Recent emerging evidence indicates a role for food-induced mucosal alterations in the pathogenesis of upper GI alterations and symptoms. A number of studies used confocal laser endomicroscopy to demonstrate duodenal mucosal reactions to food allergens in patients reported to have IBS (69)(70)(71)(72). In a preliminary report, improvement of symptoms and duodenal barrier function was observed after 6 weeks of a low FODMAP diet in FD (73).…”

“…A likely prerequisite for duodenal reactions to mucosally applied nutrients is increased mucosal permeability (77,78). In both the confocal laser endomicroscopy and in the 6 food elimination diet studies, similar to the IBS studies, patients were negative on blood tests for classical immunoglobulin E (IgE)-mediated food allergies (69–72,75,76). One hypothesis is local production of food-targeting IgEs (79), but to date there are no reports that have evaluated this possibility in the upper GI tract.…”