Researchers have identified the biological mechanism that explains why some people experience abdominal pain when they eat certain foods.
From: KU Leuven
January 17, 2021 -- KU Leuven
researchers have identified the biological mechanism that explains why some
people experience abdominal pain when they eat certain foods. The finding paves
the way for more efficient treatment of irritable bowel syndrome and other food
intolerances. The study, carried out in mice and humans, was published in Nature.
Up to 20% of the world's population
suffers from the irritable bowel syndrome (IBS), which causes stomach pain or
severe discomfort after eating. This affects their quality of life. Gluten-free
and other diets can provide some relief, but why this works is a mystery, since
the patients are not allergic to the foods in question, nor do they have known
conditions such as coeliac 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," 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."
Histamine
His team's laboratory and clinical
studies reveal a mechanism that connects certain foods with activation of the
cells that release histamine (called mast cells), and subsequent pain and
discomfort. Earlier work by Professor Boeckxstaens and his colleagues showed
that blocking histamine, an important component of the immune system, improves
the condition of people with IBS.
In a healthy intestine, the immune
system does not 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, such as food
poisoning, the researchers started with the idea that an infection while a
particular food is present in the gut might sensitise the immune system to that
food.
They 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. An antigen is any
molecule that provokes an immune response. Once the infection cleared, the mice
were given ovalbumin again, to see if their immune systems had become
sensitised 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.
A spectrum of food-related immune
diseases
The researchers were then able to unpick
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 the disruptive bacteria.
It did not produce more general symptoms of a food allergy.
Professor Boeckxstaens speculates that
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 food allergy, comprising a generalised
condition of severe mast cell activation, with an impact on breathing, blood
pressure, and so on."
The researchers then went on to see 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 localised immune reactions similar to that seen in
the mice. No reaction was seen in healthy volunteers.
The relatively small number of people
involved means this finding needs further confirmation, but it appears
significant when considered alongside the earlier clinical trial showing
improvement during treatment of IBS patients with anti-histaminics. "This
is further proof that the mechanism we have unravelled has clinical
relevance," Professor Boeckxstaens says.
A larger clinical trial of the
antihistamine treatment is currently under way. "But knowing the mechanism
that leads to mast cell activation is crucial, and will lead to novel therapies
for these patients," he goes on. "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."
Story Source:
Materials provided by KU Leuven. Note:
Content may be edited for style and length
https://www.sciencedaily.com/releases/2021/01/210117132238.htm
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