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However, current oral therapies remain constrained by the spatial and functional separation between intestinal inflammation and central nervous system dysfunction. Here, we present a comprehensive gut\u2010brain dual region integrated therapeutic strategy based on functionalized\n                    <jats:italic>Bifidobacterium longum<\/jats:italic>\n                    hydrogel (INPs@BL@Gel), in which baicalin and tyrosine are coordinated with Fe(III) to form infinite coordination polymers (ICPs), coated with inulin, assembled onto\n                    <jats:italic>Bifidobacterium longum<\/jats:italic>\n                    (BL), and subsequently encapsulated within a pH\u2010 and matrix metalloproteinase\u2010responsive silk fibroin\u2010gelatin hydrogel. INPs@BL@Gel exhibits high drug\u2010loading, effective gastric protection, inflammation\u2010triggered release, and long\u2010term intestinal colonization. Within the inflamed intestine, BL and components synergistically suppress inflammatory responses, restore gut microbiota homeostasis, and promote intestinal barrier repair through multi\u2010target integrated therapy. Importantly, BL combined with components markedly enhances the production of beneficial neuroactive metabolites such as homovanillic acid and short\u2010chain fatty acids, which integratedly regulate neuroinflammation, preserve synaptic function, and facilitate blood\u2010brain barrier repair via the gut\u2010brain axis. In vivo studies demonstrate that INPs@BL@Gel not only exerts potent therapeutic efficacy against colitis and effectively alleviates associated depression, but also reshapes the gut microbiota and restores barrier integrity, achieving a remarkable comprehensive therapeutic effect.\n                  <\/jats:p>","DOI":"10.1002\/advs.76242","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T19:47:41Z","timestamp":1782157661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Component Functionalized\n                    <i>Bifidobacterium Longum<\/i>\n                    Hydrogel for Multi\u2010Target Integrated Therapy of Colitis\u2010Associated Anxiety and Depression"],"prefix":"10.1002","volume":"13","author":[{"given":"Shuo","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Brain Science &amp; Department of Psychiatry The First Affiliated Hospital 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