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We May Now Know The Key Mechanism That Causes IBS

Johannes Van Zijl

Johannes Van Zijl

Managing Director

clockJan 21 2021, 11:10 UTC
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Man with painful stomach

A key mechanism that causes IBS revealed. By PopTika/Shutterstock.com

Researchers from KU Leuven have discovered a key biological mechanism behind Irritable bowel syndrome (IBS), and it may explain why some people suffer severe abdominal pain after eating certain foods. 

Between 10-20 percent of the global population might be suffering from IBS, an excruciating condition that affects the digestive system and can lead to severe pains and cramps, constipation, bloating, and even diarrhea in some people after they consume certain food types that trigger the condition.

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The cause of IBS has been largely unknown, although there have been different theories put forward – one being the condition could be partly psychological, others suggesting bacterial infections might be the culprit. Although changes in diet – like changing to a gluten-free option – often provide some relief to those suffering from the condition, it has remained unclear as to why that is the case.

Now, researchers have discovered that a locally-driven immune response against certain food particles can cause the activation of mast cells in the digestive tract, resulting in the release of histamine. Histamine is a hormone involved in the physiological regulation in the gut and could be the explanation behind the pain and discomfort experienced in IBS.  

The research, conducted on mice and humans, is published in the journal Nature.

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

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In previous work by Professor Boeckxstaens group, they have shown that if histamine production is blocked, it can improve IBS in people. This new study has investigated why this strategy might work. For people with a healthy gut, their immune systems do not naturally react to food particles, so the researchers had to find out what might cause the immune system to go astray in people with IBS. 

As a press release explained, many people suffering from IBS often describe some form of gastrointestinal dysfunction from things like food poisoning infections prior to the long term onset of IBS.  

In the study, the researchers first infected mice with a stomach bug that resulted in a gut infection. During the same period, they fed the animals ovalbumin, a type of protein found in eggs that is often used in experiments to test immune responses against food antigens.

When the animals recovered from the gut infection and were back to normal, the researchers tested their hypothesis to see what would happen if they then fed the animals ovalbumin again. They gave the protein to animals that were infected with the stomach bug prior, and to another group of animals that didn't have the gut infection prior to getting ovalbumin. As they suspected, the ovalbumin protein activated the immune system in the animals that had the gut infection earlier and resulted in mast cell activation and the release of histamine locally, whereas animals only fed ovalbumin without infection were completely fine.

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The study authors were able to unpick the biological mechanism that ultimately led to the mast cell activation and histamine release in the animals that had the infection prior. They found that mast cell activation was only present in the local part of the digestive system that was infected with the bug, and it was not an overall activation of the immune system – something more seen in food allergy reactions, for example. 

"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 generalised condition of severe mast cell activation, with an impact on breathing, blood pressure, and so on." Boeckxstaens explains. 

Knowing this, the researchers wanted to see the same holds true in people. 12 participants with IBS had common food antigens to gluten, wheat, soy, dairy, injected into their intestinal walls to see what would happen with the immune system. What the experiment revealed was a very similar localized immune response to what the authors saw in their animal work, and furthermore, this was not observed in the healthy control participants who did not have IBS.

"This is further proof that the mechanism we have unravelled has clinical relevance," Professor Boeckxstaens said.

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Although there was only a relatively small number of human participants in this study, and the fact that larger studies should be completed to confirm this in localized mast cell activation in humans, the current work illustrates a promising stepping stone for potentially having more therapeutics to treat IBS in the future. 

"But knowing the mechanism that leads to mast cell activation is crucial, and will lead to novel therapies for these patients," Boeckxstaens said. "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." he concludes.


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