Food allergy diagnoses have surged since the start of the 21st century (1). The Food and Drug Administration (FDA)’s 2020 approval of Palforzia, the first immunotherapy for childhood peanut allergy, was a welcome breakthrough (2).
Several years later, it’s become clear that Palforzia is no panacea; up to a fifth of patients discontinue the drug due to gastrointestinal side effects (3). Many patients struggle to stick to the drug’s strict dosing regimen and lose tolerance to the peanut allergen.
Now, in a new study, researchers highlighted a different route to treating food allergies (4). Their drug formulation includes a common dietary fiber supplement called inulin that interacts with gut microbes which in turn alter immune cell behavior to tolerate allergens. The therapy gave allergic mice long-lasting tolerance to common allergens such as peanuts, milk, and egg whites. The treatment targets the basic cause of food allergy rather than just suppressing its symptoms.
“There have been many reports showing the gut microbiome plays a crucial role in most immune responses in food allergy patients,” said coauthor James Moon, a biomedical engineer at the University of Michigan. Moon’s previous research targeted the gut microbiota to improve cancer immunotherapy. “We thought our approach of modulating the gut microbiome could be applicable for food allergy,” he added.
Moon’s innovation was to combine allergens with inulin, a natural carbohydrate fiber found in foods like bananas, garlic, and asparagus. His team used a heating and cooling process to turn inulin powder into a gel. “We are basically making a slurry of inulin gel together with allergen,” he explained.
Moon and his team tested their inulin formulation in a mouse model allergic to ovalbumin, a protein found in chicken eggs. Control mice had diarrhea, lost weight, and went into shock when exposed to the protein. These responses were reduced in mice given the inulin gel-allergen formulation. Changes in the mice’s gut bacteria drove these improvements, said Moon. “When microbes digest inulin, they produce microbial metabolites,” he added. These metabolites stimulated immune cells in the small intestine to release anti-inflammatory molecules.
Another beneficial factor of this approach is that inulin takes a long time to pass through the gut. “A longer retention time in the [gastrointestinal] tract allows immune cells to sample and take up allergen. So, you get much more effective delivery of allergen to immune cells,” said Moon.
Researchers have increasingly recognized the microbiota and gut as key players in the immune response, said Cathryn Nagler, an immunologist at the University of Chicago who wasn’t involved in the study. “The products of bacteria in our gut microbiota are regulating almost all aspects of our physiology,” she said.
Moon’s inulin formulation protected the mice against multiple allergens for over 100 days after stopping treatment.
The findings are promising, but Nagler pointed out that translation from mouse to human studies is not always straightforward. “Humans are not living in a controlled environment, or genetically identical, or consuming exactly the same diet,” she said.
Moon said that his team’s upcoming clinical trials will bridge the gap into humans. “We are launching the inulin gel trial in cancer patients later this year, and then after that, we will look into applying this to food allergy and other diseases,” he said.
References
- Warren, C. et al. The epidemiology of food allergy in adults. Ann Allergy Asthma Immunol 130, 276–287 (2023).
- Bird, J.A. et al. Long-term safety and immunologic outcomes of daily oral immunotherapy for peanut allergy. J Allergy Clin Immunol Glob 2, 100120 (2023).
- Brown, K.R. et al. Safety of peanut (Arachis hypogaea) allergen powder-dnfp in children and teenagers with peanut allergy: Pooled summary of phase 3 and extension trials. J Allergy Clin Immunol 149, 2043-2052.e9 (2022).
- Han, K. et al. Inulin-gel-based oral immunotherapy remodels the small intestinal microbiome and suppresses food allergy. Nat Mater, 1–12 (2024).
