Overview

• A Science study led by Arizona State University and Yale identifies specialized intestinal mast cells that, upon ingestion of allergens, produce cysteinyl leukotrienes rather than histamine.
• Blocking leukotriene synthesis with the FDA-approved asthma drug zileuton reduced symptoms and prevented the anaphylaxis-associated drop in body temperature in mouse models.
• Zileuton did not stop reactions to allergens injected into the bloodstream, underscoring that gut-initiated anaphylaxis follows a distinct, leukotriene-driven pathway.
• Analyses show gut mast cells are programmed by epithelial cues and include subtypes primed for leukotriene production, reframing how exposure route shapes allergic responses.
• Epinephrine remains the emergency standard for severe reactions as human relevance is unproven; approved leukotriene-targeting drugs such as montelukast are candidates for repurposing pending tissue studies and clinical trials.