Treating mice with butyrate, a short-chain fatty acid that is normally produced by beneficial gut microbes, prevented anaphylactic shock in allergic mice when they were exposed to peanuts after treatment. It also reduced inflammation in animals with colitis.

Researchers from the University of Chicago presented these data at the 2022 Fall Meeting of the American Chemical Society.

Part of the work has also been posted to the preprint server bioRxiv in advance of peer review.

The contribution of the gut microbiome to health and disease is by now well established. So have the identity of some of the major contributors. Among the bugs whose presence is beneficial are certain members of the Clostridia family, who produce metabolites including butyrate that help maintain gut health.

Clostridia produce butyrate through the fermentation of dietary fiber. The average fiber intake in the U.S. is now only about half of the recommended amount, and the resulting low butyrate levels likely contribute to food allergies, inflammatory bowel disease, atopic dermatitis, and other disorders with an immune component. Antibiotic treatment also affects Clostridia and can lead to an imbalance in the gut microbiome.

Supplementing the gut microbiome with butyrate is one possible way to correct the metabolite imbalance that results from low levels of Clostridia. However, getting butyrate past the stomach without its being digested has proved challenging.

Plus, it stinks. In the bioRxiv preprint, the authors wrote that "butyrate, even with enteric coating or encapsulation, possesses a foul and lasting odor and taste."

At the meeting, Jeffrey Hubbell, who is a professor in tissue engineering, vice dean, and executive officer at the University of Chicago's Pritzker School of Molecular Engineering, and his team reported on the development of micelles carrying a butyrate prodrug.

The micelles formed a suspension in liquid, which "tucked the butyrate side chains in their core and masked the foul smell and taste," explained presenter Shijie Cao, a postdoctoral scientist in the Pritzker School. By giving the outward facing head region either positive or a neutral charge, the authors further influenced where in the gut the micelles would release their cargo.

Treating animals with the micelles, Cao said, "restored their gut barrier and microbiome, and most importantly, dosing allergic mice with the micelles prevented a life-threatening anaphylactic response when they are exposed to peanuts."

Hubbell and co-author Cathryn Nagler are also co-founders of ClostraBio, which partially funded the work and aims to commercialize the technology. It is the fourth company for Hubbell, who is also co-founder of Kuros Biosurgery, Anokion, and Focal.

Hubbell noted that unlike Palforzia (Nestle Health Sciences), the first FDA-approved peanut allergy treatment, the butyrate approach is not antigen specific, "so in principle it can be broadly applied for any food allergies." Inflammatory bowel disease is another indication where the approach could be beneficial.

And while the treatment was given orally in the current studies, subcutaneous injection leads to its accumulation in lymph nodes. Hubbell said that could be useful for dampening the immune response in a more localized manner, for example, in patients with rheumatoid arthritis.