Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China.
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China.
Biomaterials. 2023 Oct;301:122274. doi: 10.1016/j.biomaterials.2023.122274. Epub 2023 Aug 12.
Inflammatory bowel disease (IBD) is characterized by the high level of reactive oxygen species (ROS) and highly dysfunctional intestinal flora. Here, a stimulation-responsive mucoadhesive probiotic Lac@HDP was rationally constructed for achieving specific adhesion of colitis site and depleting high level of ROS in inflammatory site. Briefly, Lac is Lactobacillus acidophilus, HDP is obtained by hyaluronic acid grafted with dopamine protected by phenylboric acid. Specifically, by consuming a large amount of ROS, phenyl borate group of Lac@HDP is oxidized and fractured, thus exposing the catechol hydroxyl group and obtaining strong mucosal adhesion ability, thereby significantly prolong the retention time of Lac in the inflammatory site. In the murine model of acute and chronic colitis, the stimulation-responsive mucoadhesive probiotics were significantly more effective in alleviating colitis symptoms than antioxidants and probiotics alone. In addition, the abundance and diversity of intestinal flora were increased after treatment with Lac@HDP, which was helpful to alleviate IBD. Importantly, the stimulation-responsive mucoadhesive probiotics have good biological safety in vivo, which provides the prospect of clinical application in the future.
炎症性肠病（IBD）的特征是活性氧（ROS）水平高和肠道菌群功能失调。在这里，合理构建了一种刺激响应型黏附益生菌 Lac@HDP，以实现结肠炎部位的特异性黏附和炎症部位高水平 ROS 的耗竭。简单来说，Lac 是嗜酸乳杆菌，HDP 是通过透明质酸接枝多巴胺获得的，由苯硼酸保护。具体来说，通过消耗大量的 ROS，Lac@HDP 的苯硼酸基团被氧化和断裂，从而暴露出儿茶酚羟基基团，并获得强大的黏膜黏附能力，从而显著延长 Lac 在炎症部位的保留时间。在急性和慢性结肠炎的小鼠模型中，刺激响应型黏附益生菌在缓解结肠炎症状方面比单独使用抗氧化剂和益生菌更有效。此外，Lac@HDP 治疗后增加了肠道菌群的丰度和多样性，有助于缓解 IBD。重要的是，刺激响应型黏附益生菌在体内具有良好的生物安全性，为其未来的临床应用提供了前景。
