Food Allergies Can Be Reversed by Targeting the Microbiome

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Overview: Researchers developed polymeric micelles from butyrate, a bacterial compound made by a healthy microbiome, which is effective against peanut allergies in mice.

Source: American Chemical Society

While many people with food allergies experience mild symptoms when exposed to triggering foods, some may have fatal consequences. A bacterial compound called butyrate made by healthy microbiomes has shown promise against allergic reactions in lab tests, but it’s nasty to take by mouth.

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Today, scientists describe a tastier way to deliver this compound and report that their “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 held virtually and in person from August 21 to 25, with on-demand access available from August 26 to September 26. 9. The meeting includes 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 lacks these butyrate-producing bacteria, fragments of partially digested food can leak from the gut and trigger an immune response that results in an allergic reaction.

One way to treat people with allergies would be to give them the missing insects orally or with a fecal transplant, but that hasn’t worked well in the clinic, according to Jeffrey Hubbell, Ph.D., one of the lead researchers on the project. . (PIs).

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

“But butyrate has a very bad smell, like dog poop and rancid butter, and it tastes bad too, so people wouldn’t want to take it,” says Shijie Cao, Ph.D., who will present the results at the team meeting. which is at the University of Chicago. And even if humans could choke it, butyrate would be digested before it reaches its destination in the lower gut.

To overcome these challenges, the researchers, including co-PI Cathryn Nagler, Ph.D., and Ruyi Wang, Ph.D., designed a new delivery system. They polymerized butanoyloxyethyl methacrylamide – with a butyrate group as a side chain – with methacrylic acid or hydroxypropyl methacrylamide.

The resulting polymers self-assembled into aggregates, or polymeric micelles, which packed the butyrate side chains into their core, disguising the foul odor and taste of the compound.

The researchers administered these micelles to the digestive system of mice without healthy gut bacteria or a well-functioning gut wall. After digestive juices released the butyrate into the lower gut, the inert polymers were eliminated in the stool.

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The treatment restored the gut’s protective barrier and microbiome, in part by increasing the production of peptides that kill harmful bacteria, making way for butyrate-producing bacteria.

Most importantly, dosing allergic mice with the micelles prevented a life-threatening anaphylactic reaction when exposed to peanuts.

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This shows a woman serving food
If a person’s microbiome is unhealthy and lacks these butyrate-producing bacteria, fragments of partially digested food can leak from the gut and trigger an immune response that results in an allergic reaction. Image is in the public domain

“This type of therapy is not antigen-specific,” notes Cao. “So theoretically it can be broadly applied to food allergies by modulating gut health.”

The following are trials in larger animals, 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 packet and stir the contents into a glass of water or juice. In other work with the micelles, the team is analyzing data on treating inflammatory bowel disease with the oral therapy.

The team is also investigating administration by injection. The researchers have shown that this method causes the micelles and their butyrate charge to accumulate in lymph nodes, which are part of the immune system.

They found that this approach is effective in treating peanut allergies in mice, but it can also be used to suppress immune activation locally — rather than throughout the body. For example, injections may be helpful in patients who have had an organ transplant or who have a localized autoimmune and inflammatory disease such as rheumatoid arthritis.

Financing: The researchers acknowledge the support and funding from their start-up company, ClostraBio, and the University of Chicago.

About this research news on microbiome and food allergy

Author: Katie Cottingham
Source: American Chemical Society
Contact: Katie Cottingham – American Chemical Society
Image: The image is in the public domain

Original research: The findings will be presented at ACS Fall 2022

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