The prevalence of food allergies and several other chronic inflammatory diseases has increased dramatically over the past few decades. At the same time, research in the area has increasingly linked these problems to lack of a healthy microbiome, especially in the gut.
Some of the bacteria in the gut microbiome produce metabolites that foster the growth of beneficial bacteria and maintain the lining of the gut. One such metabolite is butyrate, which has been shown to play a role in allergic reactions. For example, if a person’s microbiome lacks butyrate-producing bacteria, fragments of partially digested food can leak out of the gut and produce an immune reaction that results in an allergic response.
Treating the unhealthy microbiome with butyrate is an obvious solution, but there are practical challenges. In addition to butyrate tasting and smelling “like dog poop and rancid butter,” according to University of Chicago researcher Shijie Cao, the bacterial compound would break down before reaching the lower gut is someone managed to take it orally.
In new research presented at the fall meeting of the American Chemical Society (ACS), Cao, Jeffrey Hubbell and their team describe an improved butyrate delivery system that succeeded in preventing an anaphylactic response in mice.
According to the research team, they polymerized butanoyloxyethyl methacrylamide—which has a butyrate group as a side chain—with methacrylic acid. The resulting polymers self-assembled into polymeric micelles that tucked the butyrate side chains in their core, thus cloaking the compound’s foul smell and taste.
When given to mice with unhealthy gut microbiome, these micelles triggered an increased production of peptides that kill off harmful bacteria, making room for healthy butyrate-producing bacteria. Most importantly, the micelles prevented a life-threatening anaphylactic response in allergic mice exposed to peanuts.
“This type of therapy is not antigen specific,” said Cao. “Theoretically, it can be broadly applied to any food allergies through the modulation of gut health.”
The research team says they will move on to large animal trails next, hopefully followed by human clinical trials. Ultimately, they want to seek FDA approval for the oral treatment.
“Micelles could be marketed in small packets. Patients would tear open a packet, stir the contents into a glass of water or juice and just drink,” said Hubbell.
The micelles aren’t limited to treating just food allergies, either. The research team says they are analyzing data from preclinical models on treating inflammatory bowel diseases with the oral therapy.
They are also investigating alternative administration methods, such as injection, for other applications. The researchers have demonstrated that administration via injection allows the micelles and their butyrate cargo to accumulate in lymph nodes. While this method has already been shown to be effective in treating peanut allergies in mice, the team says it could also be used to suppress immune activation locally—rather than throughout the body. For example, injections could be helpful in patients who have had an organ transplant or who have a localized autoimmune and inflammatory condition, such as rheumatoid arthritis.