华中农业大学李家奎教授团队设计构建纳米-益生菌复合体系统为肠道疾病治疗开辟新路径

近日，我院李家奎教授团队在国际知名期刊《Materials Today Bio》上发表了题为“Tannic acid-iron stabilized probiotic silver nano hybrids: Multi-target gut microbiota modulation and intestinal barrier restoration”的研究论文。该研究创新性地设计并构建了一种集益生菌活性与纳米银抗菌功能于一体的新型生物纳米复合系统BL@TA-FeIII@AgNPs，为现有肠道炎症疗法提供了全新策略。

图 1 BL@TA-FeIII@AgNPs结构模式图

该复合材料以活性地衣芽孢杆菌（BL）为核心，通过单宁酸-铁离子（TA-FeIII）配位层包覆，并原位锚定超小尺寸银纳米颗粒（AgNPs）。表征结果证实其结构完整、胃肠道环境耐受性好且细胞毒性低。该体系在模拟胃肠液中展现出优异的益生菌保护能力和对致病菌（如大肠杆菌、金黄色葡萄球菌）的有效杀灭活性。在脂多糖（LPS）诱导的小鼠肠道损伤模型中，BL@TA-FeIII@AgNPs展现出显著的肠道保护与修复功效：有效降低小鼠炎症、改善肠道屏障损伤、降低氧化损伤标志物丙二醛水平。尤为关键的是，通过16S rRNA基因测序和非靶向代谢组学（LC-MS/MS）分析盲肠内容物发现，该复合系统能显著重塑紊乱的肠道菌群结构和代谢物网络。综合体内外生物安全性评估表明其耐受性良好，并能有效修复LPS诱导的肠道屏障损伤，恢复肝脏抗氧化能力。该研究证明BL@TA-FeIII@AgNPs通过巧妙融合益生菌功能与纳米技术，实现了抗菌、抗炎、靶向递送与微生态调节的多效协同，为恢复肠道稳态、屏障完整性和抑制氧化炎症级联反应提供了强大且安全的治疗潜力。这一突破性成果标志着纳米医学与微生物组疗法在应对复杂胃肠道疾病领域的重要融合，为开发下一代肠道炎症治疗药物提供新的思考角度。

图 2 BL@TA-FeIII@AgNPs对LPS引起的损伤的保护作用

我院博士生龚赛赛、曾智博为共同第一作者，我院李家奎教授、化学院鲁哲学副教授和我院博士后Muhammad Fakhar-e-Alam kulyar为共同通讯作者。论文相关研究工作得到现代农业产业技术体系和西藏自治区重点研发项目的资助。

论文摘要如下：

The limited efficacy and adverse effect profile of current pharmacological treatments for intestinal inflammation underscore the need for modalities that preserve gut microbiota balance while attenuating inflammation. The aim of this study was to develop and evaluate a BL@TA-FeIII@AgNPs system with a view to provide synergistic efficacy against intestinal injury. This research introduces an innovative hybrid bio nanocomposite, BL@TA-FeIII@AgNPs, comprising viable Bacillus licheniformis coated with a tannic-acid/FeIII coordination layer that nucleates and anchors 7 ± 1.5 nm silver nanoparticles. Characterization of this composite material was performed using TEM, EDS, XRD, and XPS. Functional assays included probiotic viability, tolerance to simulated gastric and intestinal fluids, and bactericidal activity against Escherichia coli and Staphylococcus aureus. In-depth safety evaluations were carried out using both cell cultures and a mouse model. Therapeutic effects in an acute LPS-endotoxemia mouse model were analyzed by 16S rRNA gene amplicon sequencing and untargeted LC-MS/MS metabolomics of cecal contents. Characterization confirmed structural integrity, colloidal stability in physiological media, and low cytotoxicity (IC50 > 100 μg Ag mL−1). BL@TA-FeIII@AgNPs restored transepithelial electrical resistance, lowered malondialdehyde levels, and reshaped microbiota composition and metabolite networks relative to LPS controls. Restoration of the Firmicutes: Bacteroidetes ratio and elevated short chain fatty acid concentrations support BL@TA-FeIII@AgNPs as a promising adjunctive strategy for acute endotoxin-induced intestinal injury.

论文链接: https://doi.org/10.1016/j.mtbio.2025.10210

（日程截止至7.18，以现场实际公布为准）

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来源：华中农业大学

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