Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, P. R. China.
Adv Mater. 2020 Nov;32(45):e2004529. doi: 10.1002/adma.202004529. Epub 2020 Oct 1.
While microbial-based therapy has been considered as an effective strategy for treating diseases such as colon cancer, its safety remains the biggest challenge. Here, probiotics and prebiotics, which possess ideal biocompatibility and are extensively used as additives in food and pharmaceutical products, are combined to construct a safe microbiota-modulating material. Through the host-guest chemistry between commercial Clostridium butyricum and chemically modified prebiotic dextran, prebiotics-encapsulated probiotic spores (spores-dex) are prepared. It is found that spores-dex can specifically enrich in colon cancers after oral administration. In the lesion, dextran is fermented by C. butyricum, and thereby produces anti-cancer short-chain fatty acids (SCFAs). Additionally, spores-dex regulate the gut microbiota, augment the abundance of SCFA-producing bacteria (e.g., Eubacterium and Roseburia), and markedly increase the overall richness of microbiota. In subcutaneous and orthotopic tumor models, drug-loaded spores-dex inhibit tumor growth up to 89% and 65%, respectively. Importantly, no obvious adverse effect is found. The work sheds light on the possibility of using a highly safe strategy to regulate gut microbiota, and provides a promising avenue for treating various gastrointestinal diseases.
虽然基于微生物的疗法已被认为是治疗结肠癌等疾病的有效策略，但它的安全性仍是最大的挑战。在这里，将具有理想生物相容性且广泛用作食品和药物产品添加剂的益生菌和益生元结合起来构建安全的微生物群调节材料。通过商用丁酸梭菌与化学修饰的益生元葡聚糖之间的主客体化学作用，制备了包封益生菌孢子的益生元（孢子-葡聚糖）。研究发现，口服后，孢子-葡聚糖可以特异性地富集在结肠癌中。在病变部位，葡聚糖被丁酸梭菌发酵，从而产生抗癌短链脂肪酸（SCFAs）。此外，孢子-葡聚糖调节肠道微生物群，增加 SCFA 产生菌（如真杆菌属和罗斯伯里氏菌属）的丰度，并显著增加微生物群的整体丰富度。在皮下和原位肿瘤模型中，载药孢子-葡聚糖分别抑制肿瘤生长达 89%和 65%。重要的是，没有发现明显的不良反应。这项工作为利用高度安全的策略来调节肠道微生物群提供了可能性，并为治疗各种胃肠道疾病提供了有前景的途径。
