Two independent studies published on August 7 in Science have identified a crucial molecular signal in the gut that appears to trigger life-threatening allergic reactions to certain Food-Induced Anaphylaxis. The research, conducted in mice, focuses on leukotrienes—chemical messengers that help immune cells communicate—and suggests that blocking their activity could prevent anaphylaxis before it starts.
Key Discovery in Allergy Mechanisms
Anaphylaxis is a rapid-onset, potentially fatal allergic reaction that can occur after exposure to allergens such as peanuts, eggs, medications, or insect stings. Symptoms include swelling, difficulty breathing, and dangerously low blood pressure. Epinephrine, administered via injection or nasal spray, is the primary emergency treatment. While effective at halting anaphylaxis after it begins, it does not prevent the reaction from occurring.
Researchers from Northwestern University, Yale University, and Indiana University set out to understand what initiates food-induced anaphylaxis. Using mice repeatedly exposed to peanut or egg proteins, they found that leukotrienes in the gut play a key role in transporting allergen molecules across the intestinal lining. Once in the bloodstream, these allergens activate mast cells, immune cells that trigger the severe inflammatory cascade characteristic of anaphylaxis. Without this transport process, allergens are far less likely to cause a dangerous reaction.
Repurposing a Known Drug
The studies also tested zileuton, an existing FDA-approved asthma drug that inhibits leukotriene production. In both experiments, mice given zileuton before allergen exposure showed significantly reduced symptoms of anaphylaxis. This effect was specific to allergens entering through the digestive tract. Injected allergens, such as those from insect stings, triggered reactions through different pathways and were unaffected by leukotriene blocking.
“This is exciting because it’s not just a new molecular pathway, it’s a pathway we can already target with an approved drug,” said Stephanie Eisenbarth, immunologist at Northwestern University Feinberg School of Medicine and coauthor of one of the studies.
Preparing for Human Trials
While the findings are currently limited to animal models, researchers believe there are strong reasons to expect similar mechanisms in humans. Plans are underway for early-stage clinical trials to test whether zileuton can prevent allergen transport across the intestinal barrier in people with food allergies. The initial human studies will involve participants allergic to foods other than peanuts to minimize risk during testing.
In addition to confirming leukotrienes’ role, the research uncovered specialized mast cell populations in the gut lining, offering further clues about why food-induced anaphylaxis differs from allergic reactions to injected allergens. “The details of how allergens can trigger reactions are incredibly complex and still poorly understood,” said Nathaniel Bachtel, an immunologist at Yale University and coauthor of the second study. “But these findings make leukotrienes a promising target for further study.”
If human trials confirm the results, zileuton, or similar drugs, could become the first preventive treatment for food-triggered anaphylaxis, a breakthrough that could change allergy care for millions. “We are making progress faster now than at any point in the history of allergy research,” said Adam Williams, an immunologist at Northwestern. “And so, there’s hope.”
