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Inflammatory bowel disease (IBD), with its colonic predilection, was frequently complicated by neuropsychiatric comorbidities such as anxiety and depression. To address this, we developed a colon-targeted, prebiotic-based synergistic therapeutic system. This system integrated anti-inflammatory and antioxidative rod-shaped Mn2(Olsa) metal-organic framework (MOF) particles with a yeast β-glucan/konjac glucomannan (YG/KGM) composite gel designed to remodel the gut microenvironment. The resulting Mn2(Olsa)/Gel composite ensured sustained intestinal adhesion and retention, facilitating efficient colon-targeted delivery. It effectively alleviated hallmark pathologies of IBD, including intestinal inflammation, microbial dysbiosis, barrier disruption, oxidative stress, and immune imbalance. In addition, the treatment significantly mitigated IBD associated anxiety- and depression-like behaviors. This work establishes a novel, targeted paradigm for the combined management of IBD and its neuropsychiatric comorbidities.

This is an open access article under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0, https://creativecommons.org/licenses/by/4.0/).
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