PT  - JOURNAL ARTICLE
AU  - Ruyi Wang
AU  - Shijie Cao
AU  - Mohamed Elfatih H. Bashir
AU  - Lauren A. Hesser
AU  - Yanlin Su
AU  - Sung Min Choi Hong
AU  - Andrew Thompson
AU  - Elliot Culleen
AU  - Matthew Sabados
AU  - Nicholas P. Dylla
AU  - Evelyn Campbell
AU  - Riyue Bao
AU  - Eric B. Nonnecke
AU  - Charles L. Bevins
AU  - D. Scott Wilson
AU  - Jeffrey A. Hubbell
AU  - Cathryn R. Nagler
TI  - Microbial metabolite butyrate-prodrug polymeric micelles demonstrate therapeutic efficacy in pre-clinical models of food allergy and colitis
AID  - 10.1101/2022.05.01.490224
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.01.490224
4099  - http://biorxiv.org/content/early/2022/07/30/2022.05.01.490224.short
4100  - http://biorxiv.org/content/early/2022/07/30/2022.05.01.490224.full
AB  - The microbiome modulates host immunity and aids in maintenance of tolerance in the gut, where microbial and food-derived antigens are abundant. Modern lifestyle practices, including diet and antibiotic use, have depleted beneficial taxa, specifically butyrate-producing Clostridia. This depletion is associated with the rising incidence of inflammatory bowel diseases, food allergy, and other noncommunicable chronic diseases. 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 gut. Here, we have developed two polymeric micelle systems, one with a neutral charge (NtL-ButM) and one with a negative charge (Neg-ButM) that release butyrate from their polymeric core in different regions of the gastrointestinal tract when administered intragastrically to mice. We show that these butyrate-containing micelles, used in combination, restore a barrier-protective response in mice treated with either dextran sodium sulfate or antibiotics. Moreover, butyrate micelle treatment protects peanut-allergic mice from an anaphylactic reaction to peanut challenge and rescues their antibiotic-induced dysbiosis by increasing the abundance of Clostridium Cluster XIVa. Butyrate micelle treatment also reduces the severity of colitis in a murine model. By restoring microbial and mucosal homeostasis, these butyrate-prodrug polymeric micelles may function as a new, antigen-agnostic approach for the treatment of allergic and inflammatory disease.Competing Interest StatementC.R.N. and J.A.H. are founders and shareholders in ClostraBio, Inc, which is developing the technology described herein. R.W., S.C., M.E.H.B., D.S.W., C.R.N. and J.A.H. are inventors on patents filed by the University of Chicago describing the micelles reported herein.