Arizona State University researchers found gut mast cells trigger food allergies by releasing leukotrienes, not histamine. This breakthrough points to asthma drugs as potential treatments to prevent severe, life-threatening allergic reactions.
Researchers at Arizona State University have discovered a surprising new pathway that could transform how we prevent life-threatening food allergy reactions. Instead of histamine, a chemical called leukotrienes, released by specialized gut mast cells, drives severe allergic responses, including anaphylaxis.
The Gut’s Unique Role in Allergic Reactions
Food allergies affect over half a billion people worldwide, and in severe cases, even a tiny exposure can trigger rapid, body-wide reactions. While scientists have long studied how allergens injected into the bloodstream or encountered via stings trigger histamine-driven responses, the mechanisms behind food-triggered gut allergies remained unclear.
The new study, conducted by ASU in collaboration with Yale University and others, shows that intestinal mast cells respond differently than those elsewhere in the body. When exposed to food allergens, these gut cells release leukotrienes, lipid-based molecules that cause inflammation, constrict airways, and trigger other severe symptoms.
“Until now, we assumed that anaphylaxis worked the same way regardless of how allergens entered the body,” explains Esther Borges Florsheim, assistant professor at ASU. “Our research shows the gut follows its own chemical pathway, with leukotrienes rather than histamine driving the reaction.”
Targeting Leukotrienes: A New Therapeutic Approach
To confirm the role of leukotrienes, researchers tested zileuton, an FDA-approved asthma drug that blocks leukotriene production. The drug reduced allergic symptoms and prevented dangerous drops in body temperature — a hallmark of anaphylaxis.
Importantly, zileuton did not affect reactions triggered by injected allergens, highlighting the gut-specific nature of this pathway.
These findings suggest that existing asthma medications could potentially be repurposed to prevent or treat severe food-induced allergic reactions, offering a proactive alternative to current emergency treatments like epinephrine, which only act after a reaction begins.
Implications for Allergy Research and Treatment
This discovery not only provides a potential new avenue for treatment but also reshapes our understanding of allergic responses. How an allergen enters the body — via the gut, skin, or bloodstream — significantly influences which chemical pathways are activated.
“This finding highlights the gut as unique in sensing allergens and other environmental triggers,” says Florsheim. “It also explains why levels of food-specific antibodies alone do not reliably predict allergy risk.”
Future studies will explore whether similar mast cell populations and leukotriene-driven pathways exist in humans and whether blocking them can prevent severe food allergy events.