However, the idea of food hypersensitivity causing neuropsychiatric disorders is still controversial because of inconsistencies across studies. Differences in the types of allergies, ethnic backgrounds, dietary habits and other factors among the study participants can produce conflicting results. More importantly, some studies included those with self-reported food allergies, while others included only those with lab-confirmed food allergies. This limited investigations to only symptomatic individuals.

My laboratory tested whether food allergens could manifest as behavioral symptoms, particularly in asymptomatically sensitized individuals. We wanted to find out whether eating offending foods could lead to brain inflammation and behavioral changes after sensitization, even in the absence of other obvious severe reactions.

To minimize the individual differences found in human studies, we decided to work with mice. We sensitized mice of the same age and genetic background to the common milk allergen β-lactoglobulin, or BLG, and fed them the same diet in the same room. We found that while BLG-sensitized mice produced moderately but significantly elevated levels of IgE, they did not show immediate allergic reactions. They could even eat food containing the milk allergen for two weeks without showing any obvious symptoms, despite maintaining elevated levels of IgE. This indicated that they were asymptomatically sensitized.

We then observed whether they showed any changes in emotionally driven behavior. Because we could not ask mice how they felt, we deduced their “feelings” by noting changes from their normal, survival-oriented behavior. Mice instinctively explore their environment to search for food and shelter while avoiding potential danger. However, “anxious” mice tend to spend more time hiding to play it safe. We identified “depressed” mice by briefly holding them by the tail. Most mice will keep fighting to get out of the uncomfortable predicament, while depressed mice quickly give up.

Our experiments were designed to simulate situations where asymptomatically sensitized individuals would eat either a large amount of an offending food in one day or small amounts every day for a few weeks. We mimicked these situations by placing a large amount of the milk allergen directly into the stomach of sensitized mice with a feeding tube, or giving them an allergen-containing mouse chow to eat the allergen a little at a time.

Interestingly, BLG-sensitized mice showed anxiety-like behavior one day after receiving a large amount of the allergen. Another group of sensitized mice developed depression-like behavior after eating small amounts of allergen for two weeks. In addition, BLG-sensitized mice showed signs of brain inflammation and neuronal damage, suggesting that changes in the brain may be responsible for their behavioral symptoms.

We also investigated the long-term effect of allergen consumption by keeping BLG-sensitized mice on the allergen-containing diet for one month. We found that IgE levels declined in sensitized mice by the end of the month, indicating that continually eating small amounts of the allergen led to decreased immune responses, or “desensitization.” In contrast, signs of brain inflammation remained, suggesting that the harmful effect of allergens persisted in the brain.

Researchers have yet to study prolonged brain inflammation, or neuroinflammation, in people who are asymptomatically sensitized. In general, though, chronic neuroinflammation is a known contributor to neurodegenerative diseases, such as multiple sclerosis and Alzheimer’s disease, although the exact causes of these diseases are unknown. A better understanding of the role allergens play in neuroinflammation can help researchers clarify whether food allergens trigger chronic inflammation that can lead to these diseases.

This knowledge could be especially important for patients undergoing oral immunotherapy, an approach to allergy treatment that involves incrementally ingesting small amounts of allergens over time. The goal is to desensitize the immune system and reduce the incidence of anaphylaxis, or life-threatening allergic reactions. In 2020, the U.S. Food and Drug Administration approved a standardized form of peanut allergens to prevent anaphylaxis in eligible pediatric patients. However, its possible long-term effect on the nervous system is unknown.

Food allergens can affect the brain and behavior of seemingly asymptomatic people, making them not so asymptomatic neurologically. Considering how your brain responds to the food you eat puts a whole new meaning to the phrase “you are what you eat.”

This article is republished from The Conversation, an independent nonprofit news site dedicated to sharing ideas from academic experts. It was written by: Kumi Nagamoto-Combs, University of North Dakota. Like this article? subscribe to our weekly newsletter.

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Kumi Nagamoto-Combs receives funding from the National Institute of Allergy and Infectious Disease and the National Institute on Aging.