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A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP)<jats:sup>+<\/jats:sup>\/S100 calcium binding protein B (S100\u03b2)<jats:sup>+<\/jats:sup> enteric glial cells (EGCs) in inflamed colonic tissues and the disruption of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) observed in chronic colitis. DHA demonstrated efficacy in restoring the functionality of the dual gut barrier while concurrently attenuating intestinal inflammation. Mechanistically, DHA inhibited the transformation of GFAP<jats:sup>+<\/jats:sup> EGCs into GFAP<jats:sup>+<\/jats:sup>\/S100\u03b2<jats:sup>+<\/jats:sup> EGCs while promoting the differentiation of GFAP<jats:sup>+<\/jats:sup>\/S100\u03b2<jats:sup>+<\/jats:sup> EGCs back into GFAP<jats:sup>+<\/jats:sup> EGCs. Furthermore, DHA induced apoptosis in GFAP<jats:sup>+<\/jats:sup>\/S100\u03b2<jats:sup>+<\/jats:sup> EGCs by inducing cell cycle arrest at the G0\/G1 phase. The initial mechanism\u00a0is further validated that DHA regulates EGC heterogeneity by improving dysbiosis in colitis. These findings underscore the multifaceted therapeutic potential of DHA in ameliorating colitis by improving dysbiosis, modulating EGC heterogeneity, and preserving gut barrier integrity, thus offering promising avenues for novel therapeutic strategies for inflammatory bowel diseases.<\/jats:p>","DOI":"10.1002\/advs.202403461","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T01:40:09Z","timestamp":1720748409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis"],"prefix":"10.1002","volume":"11","author":[{"given":"Peishan","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Zhongnan Hospital of Wuhan University  Wuhan 430071 China"},{"name":"Hubei Clinical Center &amp; Key Lab of Intestinal &amp; Colorectal Diseases  Wuhan 430071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Zhongnan Hospital of Wuhan University  Wuhan 430071 China"},{"name":"Hubei Clinical Center &amp; 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