Food allergies affect more than 500 million people around the world.
For many of these people, eating even a tiny amount of the wrong food can lead to a serious reaction called anaphylaxis.
This reaction can make it hard to breathe, lower blood pressure quickly, and even cause death if not treated in time.
Scientists have known for years how allergens that enter the body through injections, such as insect stings or lab tests, can trigger anaphylaxis. However, they didn’t fully understand how this dangerous reaction starts when someone eats an allergen.
Now, researchers from Arizona State University and Yale University, along with other partners, have made an important discovery. They found that certain immune cells in the gut, or digestive system, play a big role in triggering this reaction.
These special immune cells release chemical messengers that can cause the muscles in the airways and gut to tighten, create more mucus, and increase swelling. These chemicals are already known to play a part in asthma attacks. Now, scientists have shown they are also important in food allergy reactions that start in the gut.
Their study, published in the journal Science, shows that food-triggered allergic reactions begin in a different way than those caused by injections. One of the researchers, Dr. Esther Borges Florsheim from Arizona State University, explained that scientists used to think histamine was the main cause of all anaphylaxis.
Histamine is a chemical released by mast cells, a type of immune cell, and it causes many allergy symptoms. But this study found that when allergens are swallowed, the mast cells in the gut release a different group of chemicals called leukotrienes, not histamine.
Mast cells detect allergens using antibodies known as IgE. When this happens in the blood, they release histamine. That’s why antihistamines are sometimes helpful. But in the gut, mast cells respond by releasing leukotrienes, which are known to cause airway narrowing in asthma.
The gut mast cells are different from mast cells in other parts of the body. The cells that line the gut give signals to nearby mast cells, making them produce more leukotrienes. The researchers also found that gut mast cells are specially designed to do this, which helps explain why food allergies can be so serious.
To confirm that leukotrienes were the real cause of the reaction, the team tested a drug called zileuton. This medicine is already used to treat asthma and blocks the production of leukotrienes.
When used in their tests, it helped reduce allergy symptoms and protected against the dangerous drop in body temperature linked to anaphylaxis. However, it only worked for food-related allergies, not for allergies caused by injections. This shows that the gut has a unique allergic pathway with its own chemical drivers.
Today, emergency treatments for allergic reactions include epinephrine, which helps stop symptoms fast. Antihistamines are also used but are not very helpful in stopping food-related anaphylaxis. The new research suggests that targeting leukotrienes may be a better way to prevent or treat these dangerous food reactions.
More studies are needed to see if this approach will work in people. But because drugs like zileuton and montelukast (another asthma drug) are already approved, testing this idea in humans could happen sooner rather than later.
This discovery could change the way scientists think about food allergies. It shows that the way allergens enter the body — through the skin, bloodstream, or gut — affects the type of immune response. The study may also explain why doctors cannot always predict how serious a food allergy will be just by looking at IgE antibody levels.
Dr. Florsheim said this research shows the gut responds in its own special way to allergens, and possibly to other things we eat like food additives. The team now plans to study whether the same kind of mast cells and leukotriene responses happen in human guts and whether blocking this pathway can protect people with food allergies.
This study provides hope that one day, people with life-threatening food allergies may have better ways to avoid serious reactions before they start.
The study is published in Science.
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