| Feb 19, 2026 |
Oral polysaccharide-engineered nanozyme treats colitis-linked mental disorders by targeting oxidative stress and gut dysbiosis via the microbiome-gut-brain axis.
(Nanowerk News) Collaborative research teams from Yangzhou University and Nanjing University have developed an oral polysaccharide-engineered nanozyme to treat colitis-associated mental disorders. The study (Advanced Materials, “Polysaccharide Engineered Nanozymes Target Inflammation for Alleviating Colitis-Associated Mental Disorders via Microbiome-Gut–Brain Axis”), led by Dr. Gen Wei, shows that this nanozyme alleviates neuropsychiatric symptoms by modulating the microbiome–gut–brain axis, offering a promising strategy for managing colitis and its comorbidities.
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Mental disorders such as anxiety and depression affect 1.1 billion people worldwide and are rising rapidly, particularly among young individuals. These conditions arise from complex interactions among genetic, neurochemical, and environmental factors.
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Colitis provides a compelling example of this interplay, as it is strongly associated with neuropsychiatric comorbidities: nearly one-quarter of patients experience depression and one-third suffer from anxiety. This clinical link is mediated through the microbiome–gut–brain axis, where intestinal inflammation, microbial dysbiosis, and disrupted vagal signaling converge to create a bidirectional pathological connection between gut disease and mental disorders. Developing therapies that target this axis is therefore an urgent priority.
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Current treatments—including aminosalicylates, corticosteroids, immunosuppressants, and antidepressants—typically act on single pathways and often provide limited benefit. Long-term use can also lead to adverse effects and nonspecific toxicity. At the mechanistic level, reactive nitrogen and oxygen species (RNOS) drive oxidative stress and inflammation along the gut–brain axis, while microbial imbalance reduces beneficial metabolites and exacerbates neuroinflammation. An ideal strategy would localize treatment to inflamed tissue while combining antioxidant, anti-inflammatory, and microbiota-modulating functions.
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Metal-based nanozymes that mimic superoxide dismutase (SOD) can interrupt the oxidative–inflammatory cycle. However, their inability to regulate gut microbiota restricts their therapeutic potential. To address this limitation, the researchers incorporated polysaccharides as prebiotic components to rebalance microbial communities. These polymers also contain abundant functional groups capable of chelating metal ions, enabling the formation of catalytic nanocomplexes that integrate RNOS scavenging with microbiota-directed therapy.
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In this work, the team selected fucoidan, a sulfated polysaccharide that provides strong negative charge for preferential binding to inflamed colon tissue and coordination sites for metal ions. Leveraging the robust RNOS-scavenging capability of cerium through reversible Ce³⁺/Ce⁴⁺ cycling, they designed fucoidan–cerium nanocomplexes (FucCeNCs) as an oral therapeutic platform.
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| Schematic illustration of the oral FucCeNCs with anti-inflammatory effects and gut microbiota-derived metabolism regulation via microbiota-gut-brain axis for the treatment of colitis-associated mental disorders. (Image: Courtesy of the researchers) (click on image to enlarge)
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Synthesized through a simple chelation process, FucCeNCs accumulate in the colon and exert dual functions: cerium ions scavenge RNOS to shift macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotypes, while fucoidan acts as a prebiotic to restore microbial balance. The resulting anti-inflammatory cytokines and microbiota-derived metabolites transmit signals along the microbiome–gut–brain axis, suppressing neuroinflammation by inhibiting glial activation and protecting neurons.
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This study represents a significant advance in the treatment of colitis-associated mental disorders through the design of a multifunctional oral nanozyme. By simultaneously targeting oxidative stress and microbial dysbiosis, FucCeNCs overcome the limitations of conventional single-target therapies and reduce systemic toxicity.
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The work provides the first demonstration that nanozymes can therapeutically modulate the microbiome–gut–brain axis to alleviate mental disorders, opening new avenues for treating inflammation-driven neuropsychiatric conditions.
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References
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1. Wei et al., Chemical Society Reviews, 2013, 42, 6060-6093.
doi:10.1039/c3cs35486e
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2. Zhang et al., Nature Reviews Methods Primers, 2024, 4, 36.
doi:10.1038/s43586-024-00315-5
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