Scientists reverse food allergies by targeting the microbiome

The researchers report that their “polymeric micelles” are efficient in opposition to peanut allergy in mice. Treatment can typically be used in opposition to many varieties of food allergies and inflammatory illnesses.

Many individuals with food allergies expertise delicate signs solely when uncovered to set off meals. However, some endure from probably deadly penalties. A bacterial compound referred to as butyrate, made out of wholesome microbiomes, has proven promise in opposition to allergic reactions in laboratory assessments. The drawback is that it’s disagreeable to take it orally. Today, scientists describe a extra enticing method to ship this compound. They additionally declare that their “polymeric micelles” are efficient in opposition to peanut allergy in mice. One day therapy can battle in opposition to many varieties of food allergies and inflammatory illnesses.

The researchers will current their findings at the fall assembly of the American Chemical Society (ACS). ACS Fall 2022 is a hybrid digital and in-person assembly August 21-25, with on-demand entry obtainable August 26-September 9. The assembly has about 11,000 displays on a large spectrum of science.

Certain micro organism that make up the intestine microbiome produce compounds like butyrate that promote the progress of helpful micro organism and defend the lining of the intestine. If an individual’s microbiome is unhealthy and there are not any butyrate-producing micro organism, partially digested food fragments can leak out of the intestine and set off an immune response, resulting in an allergic response.

One method to deal with allergy victims is to supply them with the lacking bug by oral or fecal transplant. According to Jeffrey Hubbell, Ph.D., certainly one of the challenge’s principal investigators (PI), this has not labored properly in the clinic. “So we thought, why not ship metabolites like butyrate that promote a wholesome microbiome?”

“But butyrate smells very unhealthy, like canine poop and rancid oil, and it tastes unhealthy, so individuals do not need to ingest it,” stated Shijie Cao, who offered the outcomes at the convention. for the standing group[{” attribute=””>University of Chicago. And even if people could manage to choke it down, butyrate would be digested before reaching its destination in the lower gut.

To overcome these challenges, the scientists, including co-PI Cathryn Nagler, Ph.D., and Ruyi Wang, Ph.D., designed a new delivery system. They polymerized butanoyloxyethyl methacrylamide — which has a butyrate group as a side chain — with methacrylic

The scientists are also investigating administration via injection. The researchers have shown 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 allergies in mice, but it could also be used to suppress immune activation locally — rather than throughout the body. For instance, 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.

The researchers acknowledge support and funding from their start-up company, ClostraBio, and the University of Chicago.

Title
Microbial metabolite butyrate-prodrug polymeric micelles promote gut health and treat food allergies

Abstract
The gut microbiome has myriad effects on both mucosal and systemic health. Resident commensal bacteria play a critical role in the maintenance of mucosal homeostasis, in part through their production of short-chain fatty acids, especially butyrate. Although butyrate is known to play important roles in regulating gut immunity and maintaining epithelial barrier function, its clinical translation is challenging due to its offensive odor and quick absorption in the upper gastrointestinal tract. Here, we designed two block copolymers that contain a high content of butyrate and self-assemble into water-suspendible micelles. These two copolymers consist of a hydrophilic block, poly(N-(2-hydroxypropyl) methacrylamide) or poly(methacrylic acid), with a hydrophobic block, poly(N-(2-butanoyloxyethyl) methacrylamide), thus connecting a backbone sidechain to butyrate with an ester bond. These two copolymers form micelles with either a neutral charge (NtL-ButM) or a negative charge (Neg-ButM). Each micelle releases butyrate from their polymeric core in the ileum or the cecum, respectively, after intragastric administration to mice. These polymer formulations mask the foul smell and taste of butyrate and act as carriers to release the active ingredient (butyrate) over time as the micelles transit the GI tract. Treatment with NtL-ButM in germ-free (and thus butyrate-depleted) mice up-regulated genes expressing antimicrobial peptides in the ileal epithelium. We show that these butyrate-containing micelles, used in combination, restored a barrier-protective response in mice treated with either antibiotics or dextran sodium sulfate (DSS), a chemical perturbant that induces epithelial barrier dysfunction. Twice daily intragastric administration of our butyrate-prodrug micelles ameliorates an anaphylactic response to peanut challenge in a mouse model of peanut allergy and increases the abundance of bacteria in a cluster (Clostridium Cluster XIVa) known to contain butyrate-producing taxa. By restoring microbial and mucosal homeostasis, these butyrate-prodrug polymeric micelles may function as a new, antigen-agnostic approach to the treatment of food allergy.

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