summary: Researchers developed polymeric micelles of butyrate, a bacterial compound made by a healthy microbiome, effective against peanut allergies in mice.
Source: American Chemical Society
Although many people with dietary allergies experience mild symptoms when exposed to triggering foods, some face potentially fatal consequences. A bacterial compound called butyrate that is made by a healthy microbiome has shown promise against allergies in laboratory tests, but taking it orally is bad.
Today, scientists describe a more palatable way to deliver this compound and report that their “polymeric micelles” are effective against peanut allergies in mice. Treatment may someday counteract a variety of food allergies and inflammatory diseases.
The researchers will present their results at the American Chemical Society (ACS) fall meeting. ACS Fall 2022 is a hybrid meeting being held virtually and in person August 21-25, with on-demand access available August 26-Sept. 9. The meeting has about 11,000 presentations on a wide range of science topics.
Certain bacteria in the gut microbiome produce metabolites, such as butyrate, that promote the growth of beneficial bacteria and maintain the lining of the gut. If a person’s microbiome is unhealthy and lacks these butyrate-producing bacteria, fragments of partially digested food can pass out of the gut and trigger an immune response that results in an allergic reaction.
One of the project’s principal investigators, Jeffrey Hubbell, Ph.D. According to the U.S., one way to treat allergy sufferers would be to provide them with the missing bug, either orally or with a fecal transplant, but this is not working well in the clinic. (PI).
“So we thought, why don’t we just take in the metabolites — like butyrate — that produce a healthy microbiome?”
“But butyrate has a very bad smell, like dog feces and rancid butter, and it also tastes bad, so people won’t want to ingest it,” said Shiji Kao, Ph.D., who is presenting the results at the meeting. , says to the team, which is at the University of Chicago. And even if people can suppress it, butyrate will be digested before reaching its destination in the lower intestine.
To address these challenges, researchers including co-PIs Katherine Nagler, PhD, and Rui Wang, PhD, designed a new delivery system. They polymerized butanyloxyethyl methacrylamide—which has a butyrate group as a side chain—with methacrylic acid or hydroxypropyl methacrylamide.
The resulting polymers self-assemble into aggregates, or polymeric micelles, that tuck the butyrate side chain into their core, thus giving off the odor and taste of the compound.
The researchers administered these micelles to the digestive tracts of mice lacking either healthy gut bacteria or a properly functioning gut lining. After the digestive juices release butyrate into the lower intestine, the inactive polymers in the stool are eliminated.
The treatment restored the gut’s protective barrier and microbiome, partly by increasing the production of peptides that kill harmful bacteria, which made room for butyrate-producing bacteria.
Most importantly, dosing allergic mice with micelles prevented a life-threatening anaphylactic reaction when exposed to peanuts.
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“This type of therapy is not antigen specific,” notes Cao. “So theoretically, this could be broadly applied to any food allergy through the modulation of gut health.”
This is followed by tests in larger animals, followed by clinical trials. If those trials are successful and the U.S. Food and Drug Administration approves the oral treatment, micelles could be sold in smaller packets; Consumers tear off a packet and mix the contents in a glass of water or juice. In other work with Micell, the team is analyzing data on treating inflammatory bowel diseases with oral therapy.
The team is also investigating the administration through injection. Researchers have shown that this method allows micelles and their butyrate cargo to accumulate in lymph nodes, which are part of the immune system.
They found that this approach is effective in treating peanut allergy in mice, but it can also be used to suppress immune activation at a local level rather than throughout the body. For example, injections may be helpful in patients who have had an organ transplant or who have localized autoimmune and inflammatory conditions, such as rheumatoid arthritis.
Financing: The researchers acknowledge support and funding from their start-up company, Clostrabio, and the University of Chicago.
About this microbiome and food allergy research news
Author: Katie Cottingham
Source: American Chemical Society
contact: Katie Cottingham – American Chemical Society
image: Image is in public domain
Basic Research: Conclusion ACS Fall 2022 . will be presented in
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