工程益生菌银纳米界面通过Wnt和趋化因子再校准实现炎症结肠的多模式修复
Engineered Probiotic-Silver Nanointerfaces Enable Multimodal Repair of Inflamed Colon via Wnt and Chemokine Recalibration.
Engineered Probiotic-Silver Nanointerfaces Enable Multimodal Repair of Inflamed Colon via Wnt and Chemokine Recalibration.
炎症性肠病的发病机制涉及上皮完整性、免疫细胞迁移和全身炎症稳态等多方面相互关联的失调,因此多功能治疗策略是一种有前景的选择。本研究在地衣芽孢杆菌(Bacillus licheniformis)模板上,于单宁酸-铁(TA-Fe)金属酚网络内构建了纳米银(Nano-Ag)复合物,并评估其在TNBS诱导结肠炎中的治疗作用。该复合物表现出良好的理化性质,包括稳定的表面结构和均匀的纳米银沉积,支持其作为生物杂化纳米治疗平台的潜在应用。体内治疗产生了剂量依赖性的保护效应,其中1 mg制剂表现出最为一致的反应。该治疗方案改善了生存率、降低了发病率、减轻了腹泻和便血、降低了疾病活动度、维持了结肠长度,并显著恢复了结肠组织架构。进一步的组织学检查显示炎症浸润减少、肝脏形态改善,表明其保护作用超出肠道范围。在分子水平上,治疗效果与LEF-1抑制、axin恢复、CXCR2和CCR7减弱以及CCR5恢复相关,这与Wnt相关上皮信号和趋化因子引导的免疫运输的协同正常化相一致。血清谱分析进一步揭示了失调趋化因子网络的广泛调节,以及与肠-肝轴和肠-肾轴功能障碍相关的生化紊乱的部分纠正。总体而言,这些发现表明该工程化生物杂化纳米银平台并非通过单一抗炎机制发挥作用,而是通过上皮修复、炎症信号和全身代谢应激的整合性重塑来实现。本研究将TA-Fe稳定的益生菌纳米银疗法确定为实验性结肠炎的一种有前景的多功能策略,并为开发下一代炎症性肠病纳米药物提供了机制框架。
The pathogenesis of inflammatory bowel disease involves interconnected failures in epithelial integrity, immune cell migration, and inflammatory homeostasis in the system, making multifunctional therapeutic approaches a promising option. In this study, we developed a Bacillus licheniformis-templated nano-silver (Nano-Ag) composite within a tannic acid-iron (TA-Fe) metal-phenolic network and evaluated its therapeutic effects in TNBS-induced colitis. The composite exhibited favorable physicochemical properties, including a stable surface architecture and uniform nanosilver deposition, supporting its potential application as a biohybrid nanotherapeutic platform. In vivo treatment produced a dose-responsive protective effect, with the 1 mg formulation showing the most consistent response. This treatment regimen improved survival, reduced morbidity, alleviated diarrhea and fecal bleeding, lowered disease activity, preserved colon length, and significantly restored colonic histoarchitecture. Further histological examination revealed reduced inflammatory infiltration and improved hepatic morphology, indicating protective effects beyond the intestine. At the molecular level, therapeutic efficacy was associated with LEF-1 suppression, axin restoration, CXCR2 and CCR7 attenuation, and CCR5 recovery, consistent with coordinated normalization of Wnt-associated epithelial signaling and chemokine-guided immune trafficking. Serum profiling further revealed broad modulation of dysregulated chemokine networks and partial correction of biochemical disturbances associated with gut-liver and gut-kidney axis dysfunction. Collectively, these findings indicate that the engineered biohybrid nano-Ag platform does not act through a single anti-inflammatory mechanism, but rather through integrated remodeling of epithelial repair, inflammatory signaling, and systemic metabolic stress. Our study identifies TA-Fe-stabilized probiotic nano-Ag therapy as a promising multifunctional strategy for experimental colitis and provides a mechanistic framework for developing next-generation nanomedicines for inflammatory bowel disease.
Muhammad Farhan Rahim, Saisai Gong, Shah Nawaz, Farah Ijaz, Shaokat Ali, Kewei Li, et al. Engineered Probiotic-Silver Nanointerfaces Enable Multimodal Repair of Inflamed Colon via Wnt and Chemokine Recalibration.. ACS applied materials & interfaces. 2026; doi:10.1021/acsami.6c07451.
Muhammad Farhan Rahim, Saisai Gong, Shah Nawaz, Farah Ijaz, Shaokat Ali, Kewei Li, et al (2026). Engineered Probiotic-Silver Nanointerfaces Enable Multimodal Repair of Inflamed Colon via Wnt and Chemokine Recalibration.. ACS applied materials & interfaces. https://doi.org/10.1021/acsami.6c07451
Muhammad Farhan Rahim, Saisai Gong, Shah Nawaz, Farah Ijaz, Shaokat Ali, Kewei Li, et al. Engineered Probiotic-Silver Nanointerfaces Enable Multimodal Repair of Inflamed Colon via Wnt and Chemokine Recalibration.[J]. ACS applied materials & interfaces, 2026 doi:10.1021/acsami.6c07451.
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