Published December 22, 2022 | Version v1
Journal article Open

Treatment of peanut allergy and colitis in mice via the intestinal release of butyrate from polymeric micelles

Description

The microbiome modulates host immunity and aids the maintenance of tolerance in the gut, where microbial and food-derived antigens are abundant. Yet modern dietary factors and the excessive use of antibiotics have contributed to the rising incidence of food allergies, inflammatory bowel disease and other non-communicable chronic diseases associated with the depletion of beneficial taxa, including butyrate-producing Clostridia. Here we show that intragastrically delivered neutral and negatively charged polymeric micelles releasing butyrate in different regions of the intestinal tract restore barrier-protective responses in mouse models of colitis and of peanut allergy. Treatment with the butyrate-releasing micelles increased the abundance of butyrate-producing taxa in Clostridium cluster XIVa, protected mice from an anaphylactic reaction to a peanut challenge and reduced disease severity in a T-cell-transfer model of colitis. By restoring microbial and mucosal homoeostasis, butyrate-releasing micelles may function as an antigen-agnostic approach for the treatment of allergic and inflammatory diseases.

Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. Additional processed data are available from the corresponding authors on request. The 16S rRNA and RNAseq raw FastQ data files are available from the National Center for Biotechnology (NCBI) Sequence Read Archive, via the accession numbers PRJNA863725 and PRJNA885957, respectively. Source data for the figures are provided with this paper.

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Additional details

Identifiers

DOI
10.1038/s41551-022-00972-5
Other
oai:uchicago.tind.io:5485

Funding

Unknown funder
ClostraBio, Inc. Sponsored Research Agreement
Unknown funder
Whitaker Foundation Fellowship

UChicago Information

Division(s)
Biological Sciences Division, Physical Sciences Division, Pritzker School of Molecular Engineering
Department(s)
Cancer Biology, Chemistry, Immunology, Microbiology, Pathology, Pediatrics
Center(s) or Institute(s)
Duchossois Family Institute