Many people with dietary allergies may have minor symptoms when they consume foods that trigger them, but for some, the consequences could be lethal. In lab experiments, a bacterial chemical called butyrate produced by healthy microbiomes has shown promise in preventing allergy reactions, but it is unpleasant to consume.
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Today, researchers explain a more palatable method of administering this substance and reveal that their “polymeric micelles” successfully treat mouse peanut allergies. The therapy may one day be able to cure various inflammatory illnesses and food sensitivities.
The researchers will present their findings at the American Chemical Society’s (ACS) fall meeting. ACS Fall 2022 is a hybrid conference that will be held online and in person from August 21 to 25, with on-demand access available from August 26 to September 9. Nearly 11,000 talks covering a wide range of science issues are included in the meeting.
Some of the bacteria that make up the gut microbiome create compounds like butyrate, which promote the development of good bacteria and preserve the integrity of the gut lining. Food particles that have not been fully digested can escape the gut if the microbiome of the individual is sick and deficient in these butyrate-producing bacteria, which might trigger an allergic reaction.
The missing bugs may be given to allergy sufferers orally or by a fecal transplant, but Jeffrey Hubbell, PhD, one of the project’s principal investigators, claims that this approach has not been successful in the clinic.
So we thought why don’t we just deliver the metabolites—like butyrate—that a healthy microbiome produces?”
Jeffrey Hubbell, PhD., Study Principal Investigator, University Of Chicago
“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, PhD, who is delivering the results at the team conference at the University of Chicago. Even if humans were able to suffocate it, butyrate would be metabolized before reaching its goal in the lower stomach.
To address these issues, the scientists developed a new delivery system with co-PI Cathryn Nagler, PhD, and Ruyi Wang, PhD.
They polymerized butanoyloxyethyl methacrylamide with methacrylic acid or hydroxypropyl methacrylamide, which possesses a butyrate group as a side chain. The resultant polymers self-assembled into aggregates, or polymeric micelles, which tucked the butyrate side chains into their core, masking the compound’s terrible odor and taste.
The micelles were delivered to the digestive systems of mice that lacked either healthy gut bacteria or a properly functioning gut lining. The inert polymers were removed in the feces when digestive processes produced butyrate in the lower gut.
The treatment rebuilt the gut’s protective layer and microbiome, in addition to increasing the synthesis of peptides that kill off dangerous bacteria, allowing butyrate-producing bacteria to thrive.
Most notably, administering the micelles to allergic mice prevented a potentially fatal anaphylactic reaction when they were subjected to peanuts.
“This type of therapy is not antigen-specific. So theoretically, it can be broadly applied to any food allergies through the modulation of gut health,” Cao notes.
Trials in larger animals are next, preceded by clinical trials. If the studies are successful and the FDA approves the oral treatment, the micelles may be distributed in little packets; users would tear open a packet and swirl the contents into a glass of water or juice. In other work with micelles, the team is analyzing data on oral therapy for inflammatory bowel disease.
The team is also looking into injectable administration. The researchers demonstrated that by using this strategy, micelles and their butyrate cargo could collect in lymph nodes, which are part of the immune system.
They discovered that this method works well in treating peanut allergies in mice, but it could also be used to suppress immune activation locally rather than throughout the body. Injections, for instance, could be beneficial in individuals who have undergone an organ transplant or who have localized autoimmune and inflammatory illnesses like rheumatoid arthritis.