Targeting the microbiome could reverse food allergies

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Although many people with food allergies experience mild symptoms when exposed to trigger foods, some face potentially fatal consequences. A bacterial compound called butyrate that is produced by healthy microbiomes has shown promise against allergic reactions in lab tests, but it’s unpleasant to take orally. Today, scientists describe a more palatable way to administer this compound and report that its “polymeric micelles” are effective against peanut allergies in mice. The treatment could one day counteract many types of food allergies and inflammatory diseases.

The researchers will present their results at the fall meeting of the American Chemical Society (ACS). ACS Fall 2022 is a hybrid meeting taking place virtually and in person August 21-25, with on-demand access available August 26-September 2. 9. The meeting features nearly 11,000 presentations on a wide range of scientific topics.

Some of the bacteria in the gut microbiome produce metabolites, such as butyrate, that encourage the growth of beneficial bacteria and maintain the lining of the intestine. If a person’s microbiome is unhealthy and lacks these butyrate-producing bacteria, partially digested food fragments can leak out of the intestine and cause an immune reaction that results in an allergic response.

One way to treat people with allergies would be to provide them with the missing bugs orally or with a fecal transplant, but that hasn’t worked well in the clinic, according to Jeffrey Hubbell, Ph.D., one of the project’s principal investigators. . (PI). “So we thought, why don’t we deliver the metabolites, like butyrate, that produce a healthy microbiome?”

“But butyrate has a very bad smell, like dog poop and rancid butter, and it also tastes bad, so people wouldn’t want to swallow it,” says Shijie Cao, Ph.D., who is presenting the results at the meeting. for the team, which is at the University of Chicago. And even if people could swallow it, the butyrate would be digested before reaching its destination in the lower intestine.

To overcome these challenges, researchers including co-PI Cathryn Nagler, Ph.D., and Ruyi Wang, Ph.D., designed 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 encased the butyrate side chains in their core, thereby masking the compound’s off-flavor and odor.

The researchers administered these micelles to the digestive systems of mice that lacked healthy gut bacteria or a properly functioning intestinal lining. After digestive juices released butyrate in the lower intestine, the inert polymers were eliminated in the feces. The treatment restored the protective barrier of the gut and microbiome, in part by increasing the production of peptides that kill harmful bacteria, making room for butyrate-producing bacteria.

More importantly, dosing allergic mice with the micelles prevented a life-threatening anaphylactic response when exposed to peanuts. “This type of therapy is not antigen-specific,” Cao notes. “So, in theory, it can be broadly applied to any food allergy through modulation of gut health.”

Next are the largest animal trials, followed by clinical trials. If those trials are successful and the US Food and Drug Administration approves the oral treatment, the micelles could be marketed in small packages; consumers would tear open a package and stir the contents into a glass of water or juice. In other work with micelles, the team is analyzing data on the treatment of inflammatory bowel diseases with oral therapy.

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

This work will be presented at ACS Fall 2022, a hybrid meeting that will take place virtually and in person from August 21-25, with on-demand access available from August 26-September 2. 9.


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