Food allergies are a serious and growing problem in the West, affecting between 2 and 3 percent of adults and 4 percent of children. Many foods can cause allergic reactions, and this situation is further complicated by what is known as cross-reactions, whereby an allergy to one food can trigger an allergic reaction to another food. There are no treatments for food allergies, but researchers are working to develop and test new treatments, such as vaccines.

Food Allergies are Common

The most common causes of food allergies are peanuts, tree nuts, soy, milk, fish, shellfish, flour and eggs, and over 170 different foods have been identified as causing allergic reactions. In addition, there are those allergies that are caused by cross-reactions to other foods. Possible symptoms include itching, nausea and vomiting, skin rash, and shortness of breath with allergic shock. The exact causes of food allergies are not fully understood. Hereditary factors may play a role, as well as immune system problems. The only form of treatment is to avoid all consumption of foods to which the person is allergic. Allergens hidden in processed foods therefore pose a particular problem for food allergy sufferers. Researchers at the Norwegian Institute of Public Health have established two mouse models of food allergies to the legumes lupine and fenugreek (Trigonella foenum-graecum). These models were used to test whether legumes such as soy, peanuts, fenugreek and lupine could trigger allergic reactions in mice already allergic to lupine or fenugreek. Establishing good animal models of food allergy is important because the development of an allergic immune response depends on a complicated interaction between cell types in multiple different organs.

Established Mouse Models Could Lead to New Therapies

Lupine and fenugreek are examples of so-called “new” and “hidden” allergens that have been introduced to Norway in the last 10 to 15 years, for example in ready meals. Lupine was introduced as an addition to wheat flour in various baked goods for its ability to promote good baking. Fenugreek is used as an ingredient in foods such as curry, chutney and spiced tea and is well known in Asian dishes. Both lupine and fenugreek, unlike other legumes such as soy and peas, can cause severe cross-reactions in patients with peanut allergies. This fact was discovered as a result of reports sent to the Food Allergy Registry and these discoveries contributed to the EU making the labeling of lupins mandatory as an ingredient in food.

New therapies can be tested on the established mouse models, for example vaccines against food allergies. A vaccine must be tested in animals before it can be tested in humans, both to find out if it works and to make sure it doesn’t cause serious side effects. New foods that are brought onto the market can also be tested for allergies. Mice can be used for this purpose because their immune systems are well understood and relatively similar to humans. This means researchers can study the clinical, anaphylactic (shock) responses associated with food allergies in mice to gain a better understanding of the mechanisms that cause allergic reactions in humans.

Certain Bacterial Compound as a Protection Against Food Allergies

Although many people with food allergies experience only mild symptoms when consuming specific foods, some can have potentially fatal consequences. A bacterial compound called butyrate, made by healthy microbiomes, has shown promise in lab tests against allergic reactions, but it’s uncomfortable to take orally. Scientists seem to have found a more palatable way to administer this compound and report that its “polymeric micelles” are effective against peanut allergy in mice. The treatment could one day counteract many types of food allergies and inflammatory diseases. The researchers presented their findings at the American Chemical Society (ACS) fall meeting.

Some of the bacteria in the gut microbiome produce metabolites, such as butyrate, that promote the growth of beneficial bacteria and maintain the gut lining. When a person’s microbiome is unhealthy and lacking these butyrate-producing bacteria, fragments of partially digested food can leak out of the gut and trigger an immune response that leads to an allergic reaction. One way to treat allergy sufferers would be to give them the missing organisms orally or with a stool transplant, but that doesn’t work well in practice. For this reason, butyrate could be an alternative. However, the compound has a bad odor and taste, which is why it is not ingested by humans.

Protective Barrier of the Intestine can be Restored

To overcome these challenges, the researchers developed a new delivery system. They polymerized butanoyloxyethyl methacrylamide—which has a butyrate group as a side chain—with methacrylic acid or hydroxypropyl methacrylamide. The resulting polymers self-assembled into aggregates, or polymeric micelles, that tucked the butyrate side chains into their core, masking the compound’s foul odor and taste. The researchers administered these micelles to the digestive systems of mice that lacked either healthy gut bacteria or a properly functioning gut lining. After digestive juices released the butyrate in the lower intestine, the inert polymers were excreted in the stool. The treatment restored the gut’s protective barrier and microbiome, in part by increasing the production of peptides that kill harmful bacteria, making room for butyrate-producing bacteria.

Most importantly, administering the micelles to allergic mice prevented a life-threatening anaphylactic reaction when exposed to peanuts. Next up are trials on larger animals, followed by clinical trials. If these studies are successful and the U.S. If the Food and Drug Administration approves oral treatment, the micelles could be marketed in small packages. In other work with the micelles, the team is analyzing data on treating inflammatory bowel disease with oral therapy.

The team is also investigating administration by injection. The researchers showed that this method allows the micelles and their butyrate cargo to accumulate in lymph nodes, which are part of the immune system. They found this approach to be effective in treating peanut allergy in mice, but it could also be used to suppress immune activation locally. For example, injections could be helpful in patients who have had an organ transplant or who have a localized autoimmune and inflammatory disease such as rheumatoid arthritis.

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