Study uncovered the mechanism behind irritable bowel syndrome

The finding paves the way for more efficient treatment of irritable bowel syndrome and other food intolerances.


Irritable bowel syndrome (IBS) is a common disorder that affects the large intestine. It causes pain in the stomach, wind, diarrhoea, and constipation.

Up to 20% of the world’s population suffers from irritable bowel syndrome (IBS). The cause of irritable bowel syndrome isn’t well understood. A diagnosis is often made based on symptoms.

Now, scientists at KU Leuven have identified the biological mechanism that causes irritable bowel syndrome. In their study, scientists explain why some people experience abdominal pain when they eat certain foods. 

Professor Guy Boeckxstaens, a gastroenterologist at KU Leuven and lead author of the new research, said, “With these new insights, we provide further evidence that we are dealing with a real disease.”

Scientists uncovered a mechanism that connects certain foods with activation of the cells that release histamine (called mast cells) and subsequent pain and discomfort. In a previous study, scientists showed that blocking histamine, an essential component of the immune system, improves IBS people.

The immune system does not react to foods in a healthy intestine. Thus, at first, it was essential to discover what might cause this tolerance to breaking down.

Since people with IBS often report that their symptoms began after a gastrointestinal infection, such as food poisoning, the scientists started with the idea that an infection. In contrast, a particular food present in the gut might sensitize the immune system to that food.

For the study, scientists infected mice with a stomach bug, and at the same time, fed them ovalbumin, a protein found in egg white that is commonly used in experiments as a model food antigen.

Once the infection 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 with increased abdominal pain. This was not the case in mice that had not been infected with the bug and received ovalbumin.

Scientists later unpicked the series of events in the immune response that connected the ingestion of ovalbumin to activation of the mast cells. Significantly, this immune response only occurred in the part of the intestine infected by disruptive bacteria. It did not produce more general symptoms of a food allergy.

Professor Boeckxstaens said, “this points to a spectrum of food-related immune diseases. 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 a food allergy, comprising a generalized condition of severe mast cell activation, with an impact on breathing, blood pressure, and so on.”

Scientists later checked if people with IBS reacted in the same way. When food antigens associated with IBS (gluten, wheat, soy, and cow milk) were injected into the intestine wall of 12 IBS patients, they produced localized immune reactions similar to that seen in the mice. No response was seen in healthy volunteers.

Although the study was conducted on many people, scientists think that the study needs further confirmation. Still, it appears significant when considered alongside the earlier clinical trial showing improvement during IBS patients’ treatment with anti-histaminics.

Professor Boeckxstaens said, “This is further proof that the mechanism we have unraveled has clinical relevance.”

Journal Reference:
  1. Aguilera-Lizarraga, J., Florens, M.V., Viola, M.F. et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature, (2021). DOI: 10.1038/s41586-020-03118-2


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