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However, owing to the complex structure of the gastrointestinal tract and the influence of mucus, current small\u2010molecule and biologic\u2010based drugs for treating colitis cannot effectively act at the site of colon inflammation, and as a result, they tend to exhibit low efficacies and toxic side effects. In this study, nanogel\u2010based multistage NO delivery microcapsules are developed to achieve NO release at the inflammation site by targeting the inflammatory tissues using the nanogel. Surprisingly, oral administration of the microcapsules suppresses the growth of pathogenic bacteria and increases the abundance of probiotic bacteria. Metabolomics further show that an increased abundance of intestinal probiotics promotes the production of metabolites, including short\u2010chain fatty acids and indole derivatives, which modulate the intestinal immunity and restore the intestinal barrier via the interleukin\u201017 and PI3K\u2010Akt signaling pathways. This work reveals that the developed gas therapy strategy based on multistage NO delivery microcapsules modulates the intestinal microbial balance, thereby reducing inflammation and promoting intestinal barrier repair, ultimately providing a new therapeutic approach for the clinical management of colitis.<\/jats:p>","DOI":"10.1002\/adma.202309972","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T15:09:35Z","timestamp":1707318575000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":105,"title":["A Gas Therapy Strategy for Intestinal Flora Regulation and Colitis Treatment by Nanogel\u2010Based Multistage NO Delivery Microcapsules"],"prefix":"10.1002","volume":"36","author":[{"given":"Ya\u2010Jun","family":"Fu","sequence":"first","affiliation":[{"name":"College of Polymer Science and Engineering Sichuan University  Chengdu 610065 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