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

The gut microbiome modulates the body’s response to food antigens[1][1]. Beneficial taxa, specifically butyrate-producing Clostridia, are depleted in food-allergic individuals[2][2],[3][3]. Although butyrate is known to play important roles in regulating gut immunity and maintaining epithelial barrier function[4][4]–[6][5], its clinical translation is challenging due to its offensive odor and quick absorption in the upper gut. Here, we 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 the ileum or the cecum, respectively. 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, restore a barrier-protective response in mice treated with either dextran sodium sulfate or antibiotics. Treatment with the micelles protects peanut-allergic mice from an anaphylactic reaction to peanut challenge and rescues their dysbiosis by increasing the abundance of Clostridium Cluster XIVa. 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. ### Competing Interest Statement C.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. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-4 [5]: #ref-6