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Food allergies can be reversed by targeting the microbiome

To summarize: The researchers developed polymer micelles of butyrate, a bacterial compound made from a healthy microbiome, that was effective against peanut allergy in mice.

resource: American Chemical Society

Although many people with dietary allergies experience mild symptoms when exposed to trigger foods, some can face fatal consequences. A bacterial compound called butyrate made by a healthy microbiome has shown promise in laboratory tests against allergic reactions, but it can be annoying when taken orally.

Today, scientists describe a more palatable way to deliver the compound and report that their “polymeric micelles” are effective against peanut allergy in mice. This treatment could one day counteract many food allergies and inflammatory diseases.

The researchers will present their findings at the fall meeting of the American Chemical Society (ACS). ACS Fall 2022 is a hybrid conference that will take place August 21-25 and virtual in-person, on-demand access, from August 26-September 25. 9. The conference featured nearly 11,000 presentations on a wide range of scientific topics.

Some bacteria in the gut microbiome produce metabolites, such as butyrate, that promote the growth of beneficial bacteria and maintain the gut lining. If a person’s microbiome is unhealthy and deficient in these butyrate-producing bacteria, partially digested food fragments can leak out of the gut and mount an immune response that can lead to allergic reactions.

One of the lead researchers on the project, Dr. Jeffrey Hubbell, said one way to treat people with allergies is to give them the missing bugs by mouth or fecal transplants, but that doesn’t work well in the clinic. (PI).

“So we thought, why don’t we just provide metabolites — like butyrate — that a healthy microbiome produces?”

“But butyrate has a really bad smell, like shit and rancid butter, and it tastes so bad that people don’t want to swallow it,” said Shijie Cao, Ph.D., who presented the results at the University of Chicago. team. Even though one can suffocate it, butyrate is digested before reaching its destination in the lower digestive tract.

To overcome these challenges, researchers including PI Cathryn Nagler, Ph.D. and Ruyi Wang, Ph.D., designed a new delivery system. They polymerized butyryloxyethyl methacrylamide (which has a butyrate group in its side chain) with methacrylic acid or hydroxypropyl methacrylamide.

The resulting polymer self-assembles into aggregates or polymeric micelles, packing butyric acid side chains into its core, thereby masking the compound’s odor and taste.

The researchers administered these micelles to the digestive systems of mice lacking healthy gut bacteria or a functioning gut lining. After the digestive juices release butyrate in the lower intestinal tract, the inert polymers in the stool are eliminated.

The therapy 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 micelles to allergic mice prevented them from developing life-threatening allergic reactions when exposed to peanuts.

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If a person’s microbiome is unhealthy and deficient in these butyrate-producing bacteria, partially digested food fragments can leak out of the gut and mount an immune response that can lead to allergic reactions.Image is in the public domain

“This therapy is not antigen-specific,” Cao noted. “So in theory, it could be broadly applied to any food allergy by modulating gut health.”

Next came trials in larger animals, followed by clinical trials. If those trials are successful and the U.S. Food and Drug Administration approves the oral treatment, the micelles could be sold in small packages; consumers would tear open one 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 disease with oral therapy.

The team is also investigating drug delivery by injection. The researchers showed that this approach allowed micelles and their butyrate cargo to accumulate in lymph nodes, which are part of the immune system.

They found that this approach was effective in treating peanut allergy in mice, but it could also be used to suppress immune activation locally — not the entire body. For example, injections may be helpful in patients who have had organ transplants or have localized autoimmune and inflammatory diseases such as rheumatoid arthritis.

funds: The researchers thank their startup ClostraBio and the University of Chicago for support and funding.

About this Microbiome and Food Allergy Research News

author: Katie Cottingham
resource: American Chemical Society
touch: Katie Cottingham – American Chemical Society
picture: Image is in the public domain

Original research: Findings to be presented at ACS Fall 2022

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