By Marilynn Larkin
NEW YORK (Reuters Health) - 29/5/2019
A confocal laser endomicroscopy (CLE) analysis of patients with irritable bowel syndrome (IBS) revealed that more than half may have atypical, IgE-negative food allergies.
Dr. Detlef Schuppan of the University of Mainz told Reuters Health that IBS "is a tremendous burden on society and general health. Patients have been stigmatized, since overt signs of intestinal inflammation are absent."
"Much to our surprise, more than 50% of patients with IBS have an atypical food allergy, with negative allergen testing, but an immediate mucosal reaction, when common food allergens are applied to the upper small intestine," he said by email. "Most patients become symptom-free on exclusion of the identified allergen."
"We were stunned by the intensity of the reaction that occurs within three minutes and that we can observe and quantify real time using magnification endoscopy," coauthor Dr. Annette Fritscher-Ravens of University Hospital Schleswig-Holstein in Kiel, added by email. "The major food allergen causing IBS is wheat, followed by yeast, milk and soy - all components of our daily nutrition. Notably, patients often report abdominal complaints many hours after allergen ingestion, making a connection between food intake and abdominal problems difficult."
Drs. Fritscher-Ravens and Schuppan had previously used CLE in a feasibility study to detect patient responses to specific food components. CLE enables real-time detection and quantification of changes in intestinal tissues and cells, including increases in intraepithelial lymphocytes and fluid extravasation through epithelial leaks.
The current study expands on that work in a larger patient population, includes an analysis of duodenal biopsies and fluids from patients to investigate food reaction mechanisms, and compares results of those who did and did not have a reaction during CLE, and with healthy controls.
After exclusions and dropouts, 108 IBS patients underwent four food challenges via endoscope, followed by CLE. Biopsies and fluids were collected two weeks before and immediately following CLE.
As reported online May 14 in Gastroenterology, 76 (70%) of participants were CLE+. As Dr. Fritscher-Ravens noted, the majority (60.5%) reacted to wheat; the remainder to yeast (20%), milk (9.2%), soy (6.6%), and egg white (4%). Nine (8.3%) reacted to two of the tested food antigens.
Overall, the CLE+ patients had a four-fold increase in prevalence of atopic disorders compared with controls.
Further analyses showed that intraepithelial lymphocytes were significantly higher in duodenal biopsies from CLE+ patients, as was expression of claudin-2, compared with CLE- patients and controls.
By contrast, occludin levels were lower in CLE+ patients versus controls, and lowest in villus tips. Moreover, levels of mRNAs encoding inflammatory cytokines were unchanged in duodenal tissues after the challenges, but eosinophil degranulation increased, and levels of eosinophilic cationic protein were higher in duodenal fluid from CLE+ patients than in controls.
Drs. Fritscher-Ravens and Schuppan said they believe their findings will "improve the treatment of IBS by identifying the food allergen and allergen exclusion."
Dr. Jean Saleh, a professor of medicine (gastroenterology) at Icahn School of Medicine at Mount Sinai in New York City, told Reuters Health, "Patients with IBS have been looking for the source of their symptoms, often impugning food for etiology. No definite studies confirmed their assumption."
"The originality of this study is the objective demonstration by CLE that certain foods, when injected in the duodenum of patients with IBS, can induce an immediate reaction demonstrable by biopsies," he said by email.
The authors also "demonstrated the elevated presence of eosinophils known to respond in allergies without direct reaction of IgE (and) showed a disruption of the tight junction components and secondary alteration of the epithelial integrity responsible for the onset or aggravation of symptoms in patients with IBS," he noted.
"The study is very attractive to a research and teaching audience," Dr. Saleh said. "It may not be easily applicable as a diagnostic tool in many patients with IBS, but (may) certainly direct an effective attention to the permeability of the mucosal barrier and its objective alteration by certain foods."
Dr. Hardeep Singh, a gastroenterologist at St. Joseph Hospital in Orange, California, told Reuters Health by email the study adds to current knowledge. "Allergy testing is limited to skin testing or blood testing for specific food allergens. It's not always accurate or reliable. This study shows a new alternative that could potentially help specifically identify foods that patients are sensitive to."
That said, he added, further study is needed to see if the changes seen on CLE are reproducible clinically. "The question is, if these changes are seen microscopically, does that reliably predict that a patient has an allergy? Also, are there varying degrees of the allergy that can be quantified by CLE - i.e., can you tell if an allergy is mild, moderate or severe?"