A Future Without Food Allergies

Allergies have become an increasing concern, affecting millions of individuals and shaping the way we produce and consume food. Over the past few decades, food allergy prevalence has risen significantly, especially among children, posing severe health risks and lifestyle restrictions. The Centers for Disease Control and Prevention (CDC) reports that 5.8% of children and 6.2% of adults are affected by food allergies. Children with food allergies are at a significantly higher risk — two to four times more likely — to develop other related conditions like asthma and eczema.

With these statistics in mind, the need for effective solutions to food allergies has never been more urgent. As scientific research advances, academia and industry are collaborating to develop innovative solutions that may one day eliminate food allergies altogether. In a discussion with Tamara Hoppenbrouwers, Ph.D., an immunologist specializing in allergic responses, Kasper Hettinga, Ph.D., a food scientist exploring protein modifications in foods, and Rudy Ham-Zhu, M.S., a biotech and food tech scientist and founder of Mähmi Bio, QA examined advances that could lead to a future without food allergies.

UNDERSTANDING FOOD ALLERGIES.

Food allergies occur when the immune system mistakenly recognizes a harmless protein in food as a threat, causing a reaction. The most common allergens — peanuts, tree nuts, milk, eggs, wheat, soy, fish and shellfish — account for over 90% of all food allergy cases, according to the USDA. Symptoms can range from mild, like itching or stomach discomfort, to severe reactions, such as anaphylaxis, which can be life-threatening and requires immediate medical treatment.

Diagnosing allergies can be challenging, because reactions typically develop only after multiple encounters with an allergen, explained Hettinga, a professor in the Dairy Science and Technology Group at Wageningen University and Research.

“The first time someone is exposed to an allergen, there are no symptoms,” he said. “However, with continued exposures, the immune system can overreact and cause an allergic reaction.”

This delayed response makes it harder to diagnose allergies, especially in young children, whose immune systems are still maturing.

Sensitization to allergens typically involves the production of Immunoglobulin E (IgE) antibodies, which bind to mast cells and basophils. The next time the person eats that food, these cells release chemicals like histamine, which cause the symptoms of an allergy, such as swelling or itching. Unraveling this immune mechanism is crucial for developing treatments and technologies aimed at preventing allergic reactions.

Building on this understanding, researchers are exploring groundbreaking solutions to address food allergies. From immune response studies to innovative food processing techniques, scientists are actively working on strategies that could reshape food safety and prevent these life-threatening reactions.

PROTEIN MODIFICATION.

One approach to tackling food allergies is modifying protein structures through food processing. Research has shown that even simple heat treatments, like baking, can alter allergenic proteins.

For example, many children with milk allergies can tolerate baked milk products because the heat changes the protein structure, reducing its ability to trigger an immune response. This process alters the protein’s tertiary and quaternary structures, making it less recognizable to the immune system.

Similarly, short bursts of heat, such as microwaving apples, have been shown to reduce allergenicity in certain fruits. While this is promising, further research is necessary to ensure consistency and safety across a range of foods.

Building on this, newer processing methods are being explored as alternatives to traditional heat treatments, which could offer even more precise and effective solutions for reducing food allergenicity. Hettinga explained that one of his ongoing research projects focuses on minimizing the risks of raw milk while preserving its potential allergy-protective benefits.

“Over the past two decades, several studies have shown raw milk to have an allergy-protective effect in young children,” he said. “But as raw milk is unsafe, we are exploring alternative processes like UV-C irradiation, ultrasounds, high-pressure pasteurization and nano-second pulsed-electric-field (nano-PEF). These technologies can prevent heat-induced damage to milk proteins. In our current research, we’re investigating how milk processed with these methods is digested, how immune cells respond in vitro and testing in animal models for allergy development to see if these techniques can retain the allergy-protective benefits of raw milk.”

Among these, UV-C irradiation and nano-PEF show particular promise. Unlike traditional heat treatments, they sterilize milk without denaturing the proteins, preserving their structure and potentially maintaining their immunomodulatory effects. This means these methods could offer a safer way for allergy-prone individuals to consume dairy, while still reaping the potential benefits of raw milk.

It is fascinating to consider that something as dangerous as raw milk — known for its foodborne illness risks — might hold the key to preventing food allergies. This paradox has spurred scientists to explore ways of harnessing the allergy-protective properties of raw milk while eliminating the risks, offering new possibilities for safer, more effective allergy prevention.

GENETIC ENGINEERING.

Advances in genetic modification offer another potential breakthrough in addressing food allergies. Using CRISPR technology, scientists can edit the genes responsible for allergenic proteins, creating hypoallergenic versions. By targeting specific regions of amino acids that trigger immune responses, researchers aim to structurally alter these proteins, making them unrecognizable to the immune system. 

In some cases, proteins can also be modified to make them easier to digest, so that the digestive system breaks down potentially harmful epitopes (the parts of proteins recognized by the immune system) before they can trigger an allergic reaction.

These genetic modifications could allow for the production of foods that retain their nutritional value while eliminating allergenicity, potentially offering a long-term solution for individuals with severe allergies. However, regulatory approvals and public acceptance of genetically modified foods remain significant hurdles. The prospect of genetic engineering, particularly in relation to modifying the very DNA of foods, raises concerns among consumers, including questions about long-term health impacts and environmental considerations.

PREDICTION AND PROTEINS.

With the rise of alternative proteins from sources like algae, insects and quinoa, there is growing concern over potential new allergens. Hoppenbrouwers, an assistant professor at Wageningen University, with a joint appointment in the Food Quality and Design Group and Food and Biobased Research Group, is leading efforts to develop predictive models to address this issue.

“I’m actively working on developing an in vitro model to predict allergic sensitization to novel proteins,” she said. “There is a good chance that some of these new proteins will cause allergic responses. We are investigating multiple cell models to distinguish the responses to different proteins. For example, milk, eggs and peanuts are major allergens, while gelatin and rubisco barely cause allergic reactions. In our models, we test at least one hyperallergen and one hypoallergen and measure outcomes like cell-specific markers and cytokine secretion — the signalling molecules cells use to ‘talk’ to each other.”

In another project, Hoppenbrouwers focuses on how immune cells present protein fragments.

“When a protein or part of it is absorbed by the intestine, immune cells recognize and ‘eat’ it,” she said. “They rip it apart and present a small piece, called an epitope, on their surface. This acts as a flag that other immune cells — especially lymphocytes — recognize to activate the allergic cascade. If we can predict what epitopes from known allergens look like, we may be able to predict which epitopes from novel sources are likely to trigger allergic reactions.”

This research could lead to the development of pre-screening tools for food manufacturers to identify potential allergens in novel food products before they reach consumers.

It is fascinating to consider that something as dangerous as raw milk — known for its foodborne illness risks — might hold the key to preventing food allergies.

ENZYMATIC BREAKDOWN.

Using enzymes to break down allergenic proteins into smaller, non-reactive fragments is another strategy. Hydrolyzed infant formulas designed for babies with milk allergies are already in use, and expanding this approach could provide safe alternatives for individuals with severe food allergies.

Developing enzyme treatments that can be added to foods or taken orally, similar to lactase supplements for lactose intolerance, could be a game-changer. This approach offers convenience and immediate protection, allowing individuals to consume previously unsafe foods with reduced risk.

Current research is exploring enzyme cocktails tailored to specific allergens, which could be incorporated into food production or administered directly to individuals before meals.

PRECISION FERMENTATION.

Enzymatic breakdown of allergens is a common approach for producing hypoallergenic infant formulas, but this process often alters the organoleptic properties of hydrolyzed proteins, leading to off flavors. To mask these undesirable tastes, sweeteners are typically added.

To overcome these challenges and produce proteins with improved taste and functionality, precision fermentation has emerged as a key technology. Traditionally used to produce enzymes in products like laundry detergents, fuel ethanol and food ingredients, it has proven to be an effective tool for large-scale protein production.

During his time as a fermentation scientist at DuPont and BASF, Ham-Zhu made significant contributions to advancing this technology. Today, it is being applied to produce a broader range of proteins on a commercial scale.

However, producing proteins is only part of the solution. Just like fingerprints, each protein is unique, with distinct characteristics such as allergenicity. The UniProtKB/Swiss-Prot protein database catalogs over half a million protein sequences, highlighting this diversity. At Mähmi Bio, Ham-Zhu has developed a proprietary bioinformatics and AI platform that identifies non-allergenic proteins. By combining this cutting-edge platform with expertise in precision fermentation, Mähmi Bio is scaling the production of safe, allergen-friendly proteins, opening up new possibilities for various applications.

IMMUNOTHERAPY.

Training the immune system to tolerate allergens is another area of focus. Oral immunotherapy (OIT) is one of the most studied approaches, in which patients consume gradually increasing amounts of an allergenic food under medical supervision. Research has shown that OIT can help desensitize individuals to allergens, increasing the threshold for reactions and reducing the risk of severe responses to accidental exposure. However, it carries risks such as gastrointestinal distress and, in some cases, anaphylaxis, necessitating careful monitoring.

Other strategies include sublingual immunotherapy (SLIT) and epicutaneous immunotherapy (EPIT), which expose the body to allergens in smaller doses through the mouth or skin, respectively. Studies suggest these methods may offer safer, less invasive alternatives to OIT, though they may not achieve the same level of desensitization.

These immunotherapy approaches, while promising, each come with unique challenges and limitations. Ongoing research is crucial to refine these therapies, enhance their safety profiles and determine their long-term effectiveness.

THE ROAD AHEAD.

While these innovations show great promise, it is crucial to approach them with careful evaluation to fully understand their long-term effects. Modifying proteins may offer significant benefits, but it can also lead to unintended consequences that could affect both health and safety. 

To ensure these advancements are truly beneficial, thorough research, rigorous testing and ongoing monitoring are necessary to identify and mitigate potential risks. As our diets evolve to incorporate alternative proteins — such as algae, insects and quinoa — there is an increasing likelihood that these novel proteins could trigger allergic reactions in some individuals. This highlights the importance of conducting further research into their allergenic potential to better understand how these new foods interact with the immune system.

With continued scientific progress, coupled with robust safety protocols, the dream of a world free from food allergies is becoming more attainable. As our understanding of food allergies deepens, and as new technologies and strategies are developed, we are moving closer than ever to making this vision a reality. 

Abbey Thiel is a food scientist, YouTuber and teacher who loves sharing her passion for food science. With a background in research and education, Thiel has dedicated her career to making complex scientific concepts accessible to a wide audience.