Tackling food allergies through the microbiome? Scientists experiment with butyrate

22 Aug 2022 --- Dietary allergies can have fatal consequences, even though they are usually experienced with mild symptoms. Scientists’ experiments with the format of butyrate – a bacterial compound made of healthy microbiomes – have shown promising effects on allergic reactions. The results will be presented later this fall at the American Chemical Society (ACS) meeting.

As butyrate is unpleasant to ingest orally, the researchers are experimenting with an alternative solution, reporting that polymeric micelles are effective for peanut allergies in mice. The scientists believe the research will pave the way to counteract many inflammatory diseases and food allergies.

“Butyrate has a terrible smell and tastes bad, so people wouldn’t want to swallow it. Even if people could choke it down, butyrate would be digested before reaching its destination in the lower gut,” says Shijie Cao, a postdoc at the University of Chicago, who is presenting the results at the ACS meeting.

Enhancing beneficial bacteria
Metabolites, such as butyrate, are produced in the gut by certain bacteria that foster the growth and maintain the gut lining with beneficial bacteria. Allergic reactions can occur when fragments of partially digested food leak out of the gut.

“One way to treat those with allergies would be to provide the missing bugs to them orally or with a fecal transplant, but that hasn’t worked well in the clinic. So we thought, why don't we just deliver the metabolites like butyrate that a healthy microbiome produces?,” says Jeffrey Hubbell, one of the project’s principal investigators.

The researchers designed a new delivery system through “polymerized butanoyl oxyethyl methacrylamide which has butyrates as a side chain, with methacrylic acid or hydroxypropyl methacrylamide.”

How to overcome the taste?The scientists believe the method will pave the way for new treatments on inflammatory diseases.
The delivery system approach led to the polymers being self-assembled into polymeric micelles, tucking butyrates back into their core and cloaking bad taste and smell.

When administered to mice, the researchers used mice lacking a functional gut lining or healthy gut bacteria. Digestive juices released the butyrate, eliminating inert polymers in the feces. 

The researchers say that the treatment “restored the gut’s protective barrier and microbiome, by increasing production of peptides that kill off harmful bacteria, which made room for butyrate-producing bacteria.”

“Most importantly, dosing allergic mice with the micelles prevented a life-threatening anaphylactic response when exposed to peanuts. This type of therapy is not antigen-specific. Therefore, it can theoretically be broadly applied to any food allergies through the modulation of gut health,” notes Cao.

Previously, the gut microbiome was proven to play a significant role in food allergy prevention among infants, as well as overall health in the early years of life.

Injections and animal trials
Injection administration is one approach that benefits the immune system by accumulating lymph nodes, the researchers note. 

The scientists believe their approach could potentially suppress immune activation locally rather than through the body, especially for people who have had an organ transplant or an inflammatory condition.

Injections were also shown to be effective in peanut allergy treatment in mice. Therefore, trials in larger animals followed by clinical trials are the next step before moving forward with injections.

This also depends on the approval of the oral treatments from the US Food and Drug Administration, as the format would be small packages mixed with a beverage such as water or juice. 

Edited by Beatrice Wihlander