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New therapies could counteract food allergies and inflammatory diseases in the future
Although many people with food allergies experience mild symptoms when exposed to trigger foods, some experience potentially fatal consequences. A bacterial compound called butyrate, made by healthy microbiomes, has shown promise in laboratory tests against allergic reactions, but it is unpleasant to take orally. Today, scientists describe a more palatable way to deliver 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…
New therapies could counteract food allergies and inflammatory diseases in the future
Although many people with food allergies experience mild symptoms when exposed to trigger foods, some experience potentially fatal consequences. A bacterial compound called butyrate, made by healthy microbiomes, has shown promise in laboratory tests against allergic reactions, but it is unpleasant to take orally. Today, scientists describe a more palatable way to deliver 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 held virtually and in-person August 21-25, with on-demand access August 26-September 25. 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, which promote the growth of beneficial bacteria and maintain the intestinal lining. If a person's microbiome is unhealthy and these butyrate-producing bacteria are missing, fragments of partially digested food can leak from the intestines and cause an immune response that leads to an allergic reaction.
One way to treat allergy sufferers would be to give them 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 (PIs). “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 also tastes bad, so people wouldn't want to swallow it."
Shijie Cao, Ph.D., University of Chicago
Shijie Cao, Ph.D. presents the results at the team's meeting at the University of Chicago.
And even if people could choke it, butyrate would be digested before it reached its destination in the lower intestine.
To overcome these challenges, researchers, including co-PI Cathryn Nagler, Ph.D., and Ruyi Wang, Ph.D., 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 smell and taste.
The researchers administered these micelles to the digestive systems of mice that lacked either healthy gut bacteria or a properly functioning intestinal lining. After digestive juices released the butyrate in the lower intestine, the inert polymers were excreted in feces. 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. “This type of therapy is not antigen-specific,” notes Cao. “So in theory, by modulating gut health, it can be broadly applied to all food allergies.”
Next up are tests on larger animals, followed by clinical studies. If these 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 the micelles, the team is analyzing data on the treatment of inflammatory bowel disease with oral therapy.
The team is also studying administration via 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 that this approach is effective in treating peanut allergy in mice, but it could also be used to locally suppress immune activation -; instead of throughout the body. For example, injections could be helpful in patients who have had an organ transplant or have a localized autoimmune and inflammatory disease such as rheumatoid arthritis.
The researchers would like to thank their start-up company ClostraBio and the University of Chicago for support and funding.
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