New research at the Katholieke Universiteit (KU) Leuven in Belgium may finally uncover why some people experience irritable bowel syndrome.

Irritable bowel syndrome, or IBS for short, causes some people to feel severe discomfort or pain in their abdominal area after eating certain foods. Needless to say, it’s not pleasant. But it’s also not well understood. So the team from KU Leuven started studying the condition in a bid to get to the root of IBS and perhaps other types of food intolerance as well.

The symptoms, they explain, have to do with mast cells in our gut releasing histamines in response to certain foods.

Troublegut

“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,” says 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 findings have been confirmed in both mice and human experiments, and the authors hope they can pave the way towards new, more efficient treatment options for IBS. Up to 20% of the world’s population suffers from IBS, the team notes. Some dietary options, including gluten-free food, can help mitigate the symptoms, but we don’t know why. The mystery is only made deeper by the fact that patients with IBS aren’t allergic to these foods and don’t have conditions such as coeliac disease which could explain the reaction.

Tests in the lab revealed that certain foods can lead to the production of histamines in mast cells, which are part of the immune system. Histamines, as anyone who’s ever had to take antihistamines can attest to, are involved in allergic reactions. Earlier work by the team showed that blocking these substances does counteract symptoms for people with IBS.

First, however, the authors needed to identify the cause of the syndrome. People with IBS often report that their symptoms first started after a gastrointestinal infection, so the team started from the idea that any food present in our guts during such an infection can look like a threat to the immune system, which becomes sensitive to its presence.

In order to test their theory, they caused lab mice to contract a gastrointestinal infection and at the same time fed them ovalbumin (it literally means “egg white”), an egg-white protein commonly used as a food antigen (something that produces an immune response). After the infection cleared, the mice were given albumin again, to gauge whether their guts had become sensitized to the substance — it turns out they did. The presence of this protein was enough to induce mast cell activation, the release of histamine, leading to digestive intolerance and abdominal pain. In essence, these mice were showing IBS. Their control counterparts, who had not received ovalbumin, did not show the same reaction.

Later on, the team also pinpointed exactly where problems started in the gut: the immune response to ovalbumin only occurred in the part of the intestine infected by the disruptive bacteria. All in all they add, despite the severity of the response and the presence of histamines, the experiment did not cause the more general symptoms of food allergy to appear.

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

The next step was to test whether people with IBS reacted the same way to various known food antigens. When these were injected into the intestine wall of 12 IBS patients, they caused localized reactions similar to the ones seen in mice — but healthy volunteers didn’t show the same response.

For now, the data is still based on quite a small sample, so they do need further confirmation before we can take them as fact. But the results are still important when taken together with previous research that showed antihistamine treatments can help IBS patients. That’s enough to at least suggest that the mechanisms identified here warrant further clinical examination. One such larger-scale trial is already underway, the team explains.

“But knowing the mechanism that leads to mast cell activation is crucial, and will lead to novel therapies for these patients,” Boeckxstaens adds. “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.”

The paper “Local immune response to food antigens drives meal-induced abdominal pain” has been published in the journal Nature.