Journal
NATURE BIOMEDICAL ENGINEERING
Volume 7, Issue 1, Pages 38-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41551-022-00972-5
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The depletion of beneficial taxa in the gut, including butyrate-producing Clostridia, has led to the increase in food allergies and inflammatory bowel disease. By delivering butyrate-releasing micelles to the intestinal tract, barrier-protective responses can be restored, reducing disease severity in mouse models of colitis and peanut allergy. This approach can potentially treat allergic and inflammatory diseases by restoring microbial and mucosal homeostasis.
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.
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