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A significant challenge for the management of UC is to achieve delivery of drugs to the multi\u2010layer colonic barriers, as existing drugs are difficult to penetrate these depths. In this study, a novel drug delivery system using yeast cell wall microparticles (YPs) are developed to co\u2010encapsulate\n                    <jats:italic>Bacillus subtilis<\/jats:italic>\n                    (BS) and Rhein (Rh) termed Rh\u2010YBS. This system specifically targets colonic microfold cells, enabling direct delivery of BS to the colonic submucosa. Additionally, Rh enhances BS colonization in the submucosa through floral regulation. Studies indicate that Rh\u2010YBS can effectively reach and proliferate within the submucosa in vivo. In a DSS\u2010induced UC mouse model, Rh\u2010YBS stimulates the CGRP\u2010related neural pathway; BS activation in the submucosa leads to increased CGRP secretion, prompting goblet cells to secrete mucus and thereby repairing the mucosa. Furthermore, the Rh\u2010YBS also provide a preventive benefit against UC. In summary, Rh\u2010YBS represents an innovative drug delivery system for mucosal repair in UC treatment, activating a unique mechanism involving the CGRP\u2010related neural pathway.\n                  <\/jats:p>","DOI":"10.1002\/advs.202409711","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T03:03:45Z","timestamp":1746759825000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Colonic Submucosa Targeted Delivery of Probiotic and Rhein for Ulcerative Colitis Treatment"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4356-8336","authenticated-orcid":false,"given":"Lingqiang","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy \/ School of Modern Chinese Medicine Industry Chengdu University of Traditional Chinese Medicine  Chengdu 611130 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxin","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy \/ School of Modern Chinese Medicine Industry Chengdu University of Traditional Chinese Medicine  Chengdu 611130 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meisi","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy \/ School of Modern Chinese Medicine Industry Chengdu University of Traditional Chinese Medicine  Chengdu 611130 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy \/ School of Modern Chinese Medicine Industry Chengdu University of Traditional Chinese Medicine  Chengdu 611130 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongye","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy \/ School of Modern Chinese Medicine Industry Chengdu University of Traditional Chinese Medicine  Chengdu 611130 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dasheng","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy \/ School of Modern Chinese Medicine Industry Chengdu University of Traditional Chinese Medicine  Chengdu 611130 China"},{"name":"Chengdu Huashen Technology Group Co., Ltd.  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