Mast cells: the mechanism behind IBS

Researchers have discovered that mast cell reactions are behind irritable bowel syndrome

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Mast cells: the mechanism behind IBS

LEUVEN, Belgium—Katholieke Universiteit (KU) Leuven researchers have identified the biological mechanism that explains why irritable bowel syndrome (IBS) causes stomach pain or severe discomfort after eating. The study, entitled “Local immune response to food antigens drives meal-induced abdominal pain,” has been published in Nature.

Up to 20% of the world’s population suffers from IBS. Gluten-free and other diets can provide some relief — but why this helps is a mystery, since the patients aren’t allergic to the foods in question, and they don’t have known conditions like celiac disease.

“Very often these patients are not taken seriously by physicians, and the lack of an allergic response is used as an argument that this is all in the mind, and that they don’t have a problem with their gut physiology,” said Professor Guy Boeckxstaens, a gastroenterologist at KU Leuven, and lead author of the new research. “With these new insights, we provide further evidence that we are dealing with a real disease.”

The team’s laboratory and clinical studies revealed a mechanism that connects certain foods with activation of mast cells, which release histamine, and subsequent pain and discomfort. Earlier work by Professor Boeckxstaens and his colleagues has also shown that blocking histamine improves the condition of people with IBS.

In a healthy intestine the immune system doesn’t react to foods, so the first step was to find out what might cause this tolerance to break down. Since people with IBS often report that their symptoms began after a gastrointestinal infection like food poisoning, the researchers started with the hypothesis that an infection while a particular food is present in the gut might sensitize the immune system to that food.

Boeckxstaens and colleagues infected mice with a stomach bug, and simultaneously fed them ovalbumin, a protein found in egg white. Once the infection had cleared, the mice were given ovalbumin again, to see if their immune systems had become sensitized to it. The results were affirmative: the ovalbumin on its own provoked mast cell activation, histamine release, and digestive intolerance, as well as increased abdominal pain. This was not the case in mice that were fed ovalbumin, but had not been infected with the bug.

The researchers were then able to unpick the series of events in the immune response that connected the ingestion of ovalbumin to the activation of mast cells. They also noted that this immune response occurred only in the part of the intestine that had been infected by the disruptive bacteria, and didn’t produce more general symptoms of a food allergy.

Boeckxstaens speculated that this points to a spectrum of food-related immune diseases, and noted, “At one end of the spectrum, the immune response to a food antigen is very local, as in IBS. At the other end of the spectrum is food allergy, comprising a generalized condition of severe mast cell activation, with an impact on breathing, blood pressure, and so on.”

The researchers expanded the research by testing to see if people with IBS reacted in the same way as the mice. When food antigens associated with IBS (gluten, wheat, soy, and cow’s milk) were injected into the intestine wall of 12 IBS patients, they produced localized immune reactions similar to those seen in the mice. No reaction was seen in healthy volunteers.

The relatively small number of people tested means that this finding needs further confirmation, but the researchers believe that the results are significant when considered alongside the earlier clinical trial showing that IBS patients improved during treatment with anti-histaminics. 

“This is further proof that the mechanism we have unravelled has clinical relevance. But knowing the mechanism that leads to mast cell activation is crucial, and will lead to novel therapies for these patients,” added Boeckxstaens. “Mast cells release many more compounds and mediators than just histamine, so if you can block the activation of these cells, I believe you will have a much more efficient therapy.”

A larger clinical trial of the antihistamine treatment is currently underway.

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