Emerging evidence suggests that patients with inflammatory bowel diseases (IBDs) are predisposed to psychosocial disturbances, such as depression and anxiety. Regrettably, clinical antidepressants exhibit unsatisfactory therapeutic efficacy in IBD-associated psychosocial disturbances, primarily attributed to the inherent intestinal disorders and intricate bidirectional relationship between the gut and the brain. Herein, we report a metal–polyphenol-based antidepressant to alleviate mental disorders in dextran sulfate sodium-induced experimental acute colitis mice via modulating the microbiota–gut–brain axis. The antidepressant, termed CSMTC, comprises a core of melittin-encapsulated natural antioxidant enzymes (i.e., catalase and superoxide dismutase) and a protective shell composed of tannic acid–cerium ion network. Upon oral administration to colitis mice, CSMTC can effectively restore colonic redox balance, reinforce the intestinal barrier, modulate gut microbiota composition, maintain the blood–brain barrier integrity, and regulate systemic immune responses. Notably, behavioral test results reveal that CSMTC significantly alleviates the colitis-associated mental disorder (e.g., depression-like behavior) via the microbiota–gut–brain axis by reducing neuroinflammation, enhancing hippocampal neural plasticity, modulating hippocampal immune responses, and restoring neurotransmitter homeostasis. This work may have implications for the development of new nanodrugs for treating inflammation-associated complications.

中文翻译：

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一种基于金属-多酚的抗抑郁药，用于缓解结肠炎相关的精神障碍


新出现的证据表明，炎症性肠病 （IBD） 患者易患社会心理障碍，例如抑郁和焦虑。遗憾的是，临床抗抑郁药在 IBD 相关的社会心理障碍中表现出不令人满意的治疗效果，这主要归因于固有的肠道疾病和肠道和大脑之间错综复杂的双向关系。在此，我们报道了一种基于金属-多酚的抗抑郁药，通过调节微生物群-肠-脑轴来缓解葡聚糖硫酸钠诱导的实验性急性结肠炎小鼠的精神障碍。这种抗抑郁药称为 CSMTC，由蜂毒肽包封的天然抗氧化酶（即过氧化氢酶和超氧化物歧化酶）的核心和由单宁酸-铈离子网络组成的保护壳组成。结肠炎小鼠口服后，CSMTC 可有效恢复结肠氧化还原平衡，增强肠道屏障，调节肠道菌群组成，维持血脑屏障完整性，调节全身免疫反应。值得注意的是，行为测试结果显示，CSMTC 通过减少神经炎症、增强海马神经可塑性、调节海马免疫反应和恢复神经递质稳态，通过微生物群-肠-脑轴显着缓解结肠炎相关的精神障碍（例如，抑郁样行为）。这项工作可能对治疗炎症相关并发症的新型纳米药物的开发产生影响。