Cracking the Code of Food Allergy
New Discoveries Reveal How the Gut Triggers—and Could Help Prevent—Anaphylaxis
Cambridge, MA — Why do some people with food allergies experience life-threatening reactions, while others with the same allergy remain symptom-free?
Two groundbreaking studies, published today in Science and led by two Food Allergy Science Initiative (FASI) Principal Investigators, offer an important clue: the gut may be the deciding factor.
A Gut Reaction
The studies reveal that specialized immune cells in the gut—mast cells—play a critical role in determining the severity of allergic reactions to food. These cells release chemical signals, including one called leukotriene D4 (LTD4), which can make the gut lining more permeable. That means allergens are more likely to cross into the bloodstream and trigger anaphylaxis, a potentially fatal reaction marked by swelling, low blood pressure, and airway constriction.
Gene Clues, Chemical Signals, and a New Hope
In a study led by FASI Principal Investigator Dr. Stephanie Eisenbarth, researchers found that mice with a more active version of the enzyme DPEP1 could break down leukotriene D4 (LTD4) more effectively protecting them from severe food-allergic reactions. Mice with a less active version had higher LTD4 levels and were more vulnerable to anaphylaxis.
In a companion study FASI’s Scientific Founder and Principal Investigator Dr. Ruslan Medzhitov showed that blocking LTD4 production with the asthma drug Zileuton completely protected mice from food-induced anaphylaxis—but only when allergens were eaten, not injected. This points to the gut as a uniquely sensitive immune site requiring tailored interventions.
Together, these discoveries highlight a promising new treatment path: targeting the gut’s leukotriene signaling pathway to prevent dangerous reactions. With further research, drugs like zileuton—or new ones like it—could one day offer life-saving protection for people with food allergies.
Why It Matters
These discoveries highlight the shift in food allergy research: from thinking of it as a systemic immune disorder to recognizing the gut’s central role in driving severe allergic reactions. For families navigating food allergies, this breakthrough brings hope. It offers a clearer understanding of why reactions vary and opens the door to personalized care—based on how someone’s gut and immune cells interact with food allergens.
Science in Collaboration
This research is a result of FASI’s powerful collaborative model, bringing together top scientists from Yale University, Northwestern University, and across the FASI network.
“Understanding the biology of the gut is key to unlocking better treatments for food allergy,” said Dr. Carlos Bosques, FASI CEO. “These findings do not just explain why reactions happen—they point us toward new ways to stop them.”
Read more from Northwestern University here.
Citation:
Hoyt, L. R., Liu, E., Olson, E. C., Jacobsen, D. R., Siniscalco, E. R., Krier-Burris, R. A., Greenfield, K. G., McBride, C. D., Alfajaro, M. M., Amat, J. A. R., Zhao, Z., Xu, L., Philip, V., Verma, A., Fourati, S., Senger, D. L., Zhang, L., Bunyavanich, S., Glass, S. E., Coffey, R. J., Wilen, C. B., Williams, A., & Eisenbarth, S. C. (2025). Cysteinyl leukotrienes stimulate gut absorption of food allergens to promote anaphylaxis in mice. Science. 10.1126/science.adp0240
Bachtel, N. D., Cullen, J. L., Liu, M., Erickson, S. A., Kutyavin, V. I., El-Naccache, D. W., Florsheim, E. B., Lim, J., Sullivan, Z. A., Imaeda, R., Hudak, A., Zhang, C., & Medzhitov, R. (2025). Intestinal mast cell–derived leukotrienes mediate the anaphylactic response to ingested antigens. Science. 10.1126/science.adp0246
ARTICLE PUBLICATION DATE
7-Aug-2025
Press Contact
Food Allergy Science Initiative
About the Food Allergy Science Initiative (FASI)
The Food Allergy Science Initiative (FASI) is a nonprofit research accelerator dedicated to transforming the understanding and treatment of food allergies. By uniting leading scientists, clinicians, and innovators across disciplines—from immunology and neurobiology to microbiology and bioengineering—FASI drives high-impact discoveries that aim to deliver real-world therapies for patients. FASI funds and coordinates a collaborative research network anchored at top institutions, including several Harvard-affiliated hospitals. Committed to end-to-end science, FASI supports work from the bench to the clinic to solve one of medicine’s most urgent challenges. Learn more at foodallergyscience.org.