Can Targeting a Gut Protein Help Cure Food Allergy?

February 1, 2025 2

Targeting the intestinal protein RELMβ could restore immune tolerance and potentially prevent or cure food allergies.

Can Targeting a Gut Protein Help Cure Food Allergy?

Food can be nourishing and enjoyable, but it can also trigger allergic reactions. The key seems to be the balance of gut microbes, influenced by a protein secreted by intestinal goblet cells.

RELMβ: A Gut Protein That Turns Food into a Threat

Excess amounts of this protein, RELMβ, changes the profile of intestinal microbes in a way that cause the body not to tolerate certain triggering foods, finds a new study from Boston Children’s Hospital just published in Nature (1^✔ ✔Trusted Source
RELM&#946 Sets the Threshold for Microbiome-Dependent Oral Tolerance

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“We also showed that RELMβ is increased in children with food allergy,” says Talal Chatila, MD, who co-led the study with Seth Rakoff-Nahoum, MD, Ph.D. Emmanuel Stephen-Victor, Ph.D., in the Chatila lab and Gavin Kuziel, a Ph.D. student in the Rakoff-Nahoum, lab were co-first authors.

The good news is that RELMβ can potentially be inhibited if children are found to have it in high amounts, raising the possibility of preventing or even curing food allergy.

Preventing Food Intolerance

Through multiple studies in intestinal organoids and mouse models, the researchers found that RELMβ disrupts the body’s tolerance of triggering food antigens, and that does so by depleting certain bacterial species in the intestine that produce compounds known as indoles. The team also showed that indoles and indole derivatives — which are depleted in children with food allergy — spur the production of protective, long-lasting T regulatory cells that recognize food allergens as harmless.

Food Allergy Prevention Starts in the Gut

“RELMβ is orchestrating changes in the gut microbiome,” elaborates Chatila. “If there is too much RELMβ, it instructs goblet cells to produce anti-microbial proteins that kill the microbes that normally confer immune tolerance.”

In mice genetically prone to food allergy, blocking RELMβ soon after weaning led to production of T regulatory cells, restoring their tolerance to food allergens and preventing food allergy — and anaphylaxis — from developing later in life. The opposite was also true: giving RELMβ to mice not prone to food allergy made them allergic.

“Not only does connecting RELMβ to food allergy have therapeutic implications, but knowing which microbes RELMβ affects and how these microbes prevent food allergy can influence therapies as well,” Rakoff-Nahoum notes.

A Lasting Food Allergy Solution

The research hints at the possibility of providing a preventive treatment or cure for food allergies by restoring the immune system’s tolerance of the foods, rather than just treating the symptoms. Either RELMβ or its as-yet unidentified receptor could potentially be targeted.

“Current therapies for food allergy, such as oral immunotherapy or anti-IgE antibodies, are not known to be permanently disease-modifying,” says Rima Rachid, MD, a coauthor on the paper and director of the Food Allergy Program at Boston Children’s Hospital. “If patients stop these therapies, they become sensitized again.” There is an unmet need for therapies that, if not curative, permanently reduce the severity of allergic reactions or increase the amount of food a person can safety eat, she says.

The researchers have applied for a patent on their discoveries and plan to do more human studies to see if RELMβ is a biomarker of children at risk for food allergy. Eventually, they hope to test inhibitors of RELMβ or its receptor in clinical trials.

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