Many Patients With Irritable Bowel Syndrome Have Atypical Food Allergies Not Associated With Immunoglobulin E (2019) Fritscher-Ravens

[MSEsperanza]

Fritscher-Ravens A, Pflaum T, Mösinger M, et al. Many Patients With Irritable Bowel Syndrome Have Atypical Food Allergies Not Associated With Immunoglobulin E. Gastroenterology. 2019;157(1):109-118.e5. doi:10.1053/j.gastro.2019.03.046

https://www.gastrojournal.org/article/S0016-5085(19)34636-0/fulltext#articleInformation

Abstract
Background & aims: Confocal laser endomicroscopy (CLE) is a technique that permits real-time detection and quantification of changes in intestinal tissues and cells, including increases in intraepithelial lymphocytes and fluid extravasation through epithelial leaks. Using CLE analysis of patients with irritable bowel syndrome (IBS), we found that more than half have responses to specific food components. Exclusion of the defined food led to long-term symptom relief. We used the results of CLE to detect reactions to food in a larger patient population and analyzed duodenal biopsy samples and fluid from patients to investigate mechanisms of these reactions.

Methods: In a prospective study, 155 patients with IBS received 4 challenges with each of 4 common food components via the endoscope, followed by CLE, at a tertiary medical center. Classical food allergies were excluded by negative results from immunoglobulin E serology analysis and skin tests for common food antigens. Duodenal biopsy samples and fluid were collected 2 weeks before and immediately after CLE and were analyzed by histology, immunohistochemistry, reverse transcription polymerase chain reaction, and immunoblots. Results from patients who had a response to food during CLE (CLE+) were compared with results from patients who did not have a reaction during CLE (CLE-) or healthy individuals (controls).

Results: Of the 108 patients who completed the study, 76 were CLE+ (70%), and 46 of these (61%) reacted to wheat. CLE+ patients had a 4-fold increase in prevalence of atopic disorders compared with controls (P = .001). Numbers of intraepithelial lymphocytes were significantly higher in duodenal biopsy samples from CLE+ vs CLE- patients or controls (P = .001). Expression of claudin-2 increased from crypt to villus tip (P < .001) and was up-regulated in CLE+ patients compared with CLE- patients or controls (P = .023). Levels of occludin were lower in duodenal biopsy samples from CLE+ patients vs controls (P = .022) and were lowest in villus tips (P < .001). Levels of messenger RNAs encoding inflammatory cytokines were unchanged in duodenal tissues after CLE challenge, but eosinophil degranulation increased, and levels of eosinophilic cationic protein were higher in duodenal fluid from CLE+ patients than controls (P = .03).

Conclusions: In a CLE analysis of patients with IBS, we found that more than 50% of patients could have nonclassical food allergy, with immediate disruption of the intestinal barrier upon exposure to food antigens. Duodenal tissues from patients with responses to food components during CLE had immediate increases in expression of claudin-2 and decreases in occludin. CLE+ patients also had increased eosinophil degranulation, indicating an atypical food allergy characterized by eosinophil activation.

 

[Midnattsol]

Conclusions: In a CLE analysis of patients with IBS, we found that more than 50% of patients could have nonclassical food allergy, with immediate disruption of the intestinal barrier upon exposure to food antigens. Duodenal tissues from patients with responses to food components during CLE had immediate increases in expression of claudin-2 and decreases in occludin. CLE+ patients also had increased eosinophil degranulation, indicating an atypical food allergy characterized by eosinophil activation.

And a change in tight junction proteins which could reduce intestinal integrity and increase the immune system's contact with allergens.

 

[Kitty]

Interesting study – it's about time researchers did some proper work on this problem. It can make people's lives a misery until they figure out their trigger(s), but it's been swept aside by far too many doctors as an 'internet ailment'.

 

[Daisymay]

Very interesting and important. Those with IBS and anyone with food allergies are so often treated as if it is a MUS. More evidence that MUS is a seriously flawed concept.

 

[Peter T]

I echoed the need for more serious research on this, rather than the pointless rounds of inconclusive CBT research.

With me, avoiding certain food stuffs, drastically decreases the frequency of IBS, but I still have episodes associated with PEM and sometimes with migraines. Interestingly with migraines not associated with PEM or food intolerances, vomiting and/or an episode of IBS usually indicates the migraine is beginning to subside.

Though teasing everything apart can be confusing as some food stuffs cause simultaneously IBS, migraines and a worsening more generally of my ME symptoms. Also my food sensitivities can become more marked with PEM, and (though it is probable that my non celiac gluten intolerance started at the same time as the onset of my ME or just a month or so before the triggering viral infection) as my ME has deteriorated over the years additional intolerances have developed.

It has taken me decades to get my head around the interaction of PEM, the ME itself and food intolerances. This is not helped by the fact that the effect of the intolerances can be delayed, for example my caffeine related symptoms take four to six hours to kick in whereas gluten related symptoms takes almost exactly twenty four hours. In general services fail to equip us with tools to identify and manage the various triggers of our symptoms, other than pacing.

 

[rvallee]

There's clearly growing evidence of a pathogenic origin for the broad concept of IBS. One of the things we are learning about COVID-19 is how good it is at opening up junctions, to leak through different places. It's getting even likely that it crosses the blood-brain barrier, a very good property to have for a pathogen.

A good pathogen will be good at surviving. It will cause as little damage as possible, just enough to survive and spread elsewhere. That requires opening up junctions, there's good evidence COVID-19 does that, as do other pathogens. Syphilis is famous for lodging itself in the brain. That means opening up backdoors and crossing many protections.

It would be natural for other stuff to leak along, even by simple sheer pressure. They just happen to be at the right place at the time a junction is opened up and slip through.

We know there is an increase in bacteria in the blood in some ME patients after exertion. Things that can leak through the blood and shouldn't be there are bound to cause a reaction. Probably not the same as an allergic reaction but still, it's a foreign presence against which the immune system must act.

But it's not a linear process, it does not follow a simple step-by-step recipe. Effects can be delayed. Very hard to observe. Very easy to miss.