基于益生元的改良“盾牌”武装益生菌，增强胃肠道应激抵抗力并延长肠滞留时间，协同缓解结肠炎,ACS Nano

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基于益生元的改良“盾牌”武装益生菌，增强胃肠道应激抵抗力并延长肠滞留时间，协同缓解结肠炎
ACS Nano ( IF 15.8 ) Pub Date : 2023-07-21 , DOI: 10.1021/acsnano.3c02914
Anqi Xie ₁ , Haihua Ji ₁ , Zheyi Liu ₂ , Yiqun Wan _{1,

3} , Xuecong Zhang ₁ , Huihuang Xiong ₃ , Shao-Ping Nie ₁ , Hao Wan ₁

Affiliation

口服益生菌是缓解炎症性肠病（IBD）的一种有前途的方法。然而，胃肠道环境敏感性和益生菌肠道定植较差阻碍了缓解效果。在这里，我们开发了一种简单而有效的改良益生元“盾牌”(Fe-TA@mGN)，由 Fe ³⁺ -单宁酸交联网络和羧甲基化 β-葡聚糖组成，用于武装大肠杆菌Nissle 1917 (EcN@Fe -TA@mGN）。Fe-TA@mGN“盾牌”不仅作为动态屏障增强EcN的胃肠道应激抵抗能力，还有助于EcN在肠道定植，并与EcN协同减轻右旋糖酐硫酸钠（DSS）诱导的胃肠道应激反应。结肠炎。更具体地说，在 Fe-TA@mGN“盾牌”的保护下，暴露于模拟胃液后，武装 EcN 的存活率可能比裸 EcN 高约 1720 倍。令人兴奋的是，给药后16小时EcN@Fe-TA@mGN的肠道滞留率高达47.54±6.06%，而给药后8小时几乎所有裸露的EcN都被排出体外。凭借上述所有特性，EcN@Fe-TA@mGN 可以有效缓解结肠炎，这一点已通过肠道屏障的修复和炎症的减弱得到证实。此外，对于 EcN@Fe-TA@mGN，mGN 与 EcN 协同作用，可以积极调节肠道微生物群并促进短链脂肪酸（SCFA，特别是丁酸，维持肠道健康的主要来源）的产生，这两者将进一步促进结肠炎的缓解。我们预计，这里制定的策略将激发各种益生元的开发，以武装益生菌，以有效缓解IBD。

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Modified Prebiotic-Based “Shield” Armed Probiotics with Enhanced Resistance of Gastrointestinal Stresses and Prolonged Intestinal Retention for Synergistic Alleviation of Colitis

Oral administration of probiotics is a promising method to alleviate inflammatory bowel diseases (IBDs). However, gastrointestinal environmental sensitivity and inferior intestinal colonization of probiotics hinder the alleviation effect. Here, we developed a simple yet effective modified prebiotic-based “shield” (Fe-TA@mGN) composed of an Fe³⁺-tannic acid cross-linking network and carboxymethylated β-glucan for arming Escherichia coli Nissle 1917 (EcN@Fe-TA@mGN). The Fe-TA@mGN “shield” not only acted as a dynamic barrier to enhance the gastrointestinal stress resistance ability of EcN but also aided the intestinal colonization of EcN as well as synergized with EcN for the alleviation of dextran sulfate sodium (DSS) induced colitis. More specifically, with the protection of the Fe-TA@mGN “shield”, the survival rate of armed EcN could be up to ∼1720 times higher than that of bare EcN after exposure to simulated gastric fluid. Excitingly, the intestinal retention rate of EcN@Fe-TA@mGN was as high as 47.54 ± 6.06% at 16 h post-administration, while almost all bare EcNs were excreted out at 8 h post-administration. With all of the aforementioned attributes, EcN@Fe-TA@mGN efficiently alleviated colitis, verified by the repair of the intestinal barrier and the attenuation of inflammation. Moreover, for EcN@Fe-TA@mGN, mGN synergized with EcN to positively modulate gut microbiota and promote the production of short-chain fatty acids (SCFAs, especially for butyric acid, a primary source for maintaining intestinal health), both of which would further advance the alleviation of colitis. We envision that the strategy developed here will inspire the exploitation of various prebiotics to arm probiotics for the effective alleviation of IBD.

更新日期：2023-07-21

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