Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA.
Department of Chemistry, University of Chicago, Chicago, IL, USA.
Nat Biomed Eng. 2023 Jan;7(1):38-55. doi: 10.1038/s41551-022-00972-5. Epub 2022 Dec 22.
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.
肠道微生物组调节宿主免疫,并有助于维持肠道内的耐受性,因为这里有丰富的微生物和食物来源的抗原。然而,现代饮食因素和抗生素的过度使用导致食物过敏、炎症性肠病和其他与有益菌群(包括但不限于产生丁酸的梭菌)耗竭相关的非传染性慢性疾病的发病率上升。在这里,我们展示了通过胃内给药的中性和带负电荷的聚合物胶束,在肠道的不同区域释放丁酸,可以恢复结肠炎和花生过敏小鼠模型的屏障保护反应。用释放丁酸的胶束治疗可以增加梭菌属 XIVa 簇中产生丁酸的菌群的丰度,防止小鼠对花生的过敏反应,并减轻 T 细胞转移结肠炎模型中的疾病严重程度。通过恢复微生物和黏膜内稳态,释放丁酸的胶束可能成为一种针对过敏和炎症性疾病的抗原不可知治疗方法。