Yang Jiali, Peng Mengyun, Tan Shaochong, Ge Shengchan, Xie Li, Zhou Tonghai, Liu Wei, Zhang Kaixiang, Zhang Zhenzhong, Liu Junjie, Shi Jinjin
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, P. R. China.
Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou 450001, P. R. China.
ACS Cent Sci. 2023 Jun 21;9(7):1327-1341. doi: 10.1021/acscentsci.3c00227. eCollection 2023 Jul 26.
The effective delivery and colonization of probiotics are recommended for therapeutic interventions during colitis, the efficacy of which is hampered by abnormally colonized Enterobacteriaceae at pathological sites. To improve the delivery and colonization of probiotics, a calcium tungstate microgel (CTM)-based oral probiotic delivery system is proposed herein. CTM can selectively disrupt the ecological niche occupied by abnormally expanded Enterobacteriaceae during colitis to facilitate probiotic colonization. In addition, the calcium-binding protein, calprotectin, which is highly expressed in colitis, efficiently extracts calcium from CTM and releases tungsten to inhibit Enterobacteriaceae by displacing molybdenum in the molybdenum enzyme, without affecting the delivered probiotics. Moreover, CTM demonstrated resistance to the harsh environment of the gastrointestinal (GI) tract and to intestinal adhesion. The synergistic reduction of Enterobacteriaceae by 45 times and the increase in probiotic colonization by 25 times, therefore, result in a remarkable treatment for colitis, including restoration of colonic length, effective downregulation of the inflammatory response, restoration of the damaged mucosal barrier, and restoration of gut microbiome homeostasis.
在结肠炎的治疗干预中，推荐有效递送和定殖益生菌，但其疗效受到病理部位异常定殖的肠杆菌科细菌的阻碍。为了改善益生菌的递送和定殖，本文提出了一种基于钨酸钙微凝胶（CTM）的口服益生菌递送系统。CTM可以选择性地破坏结肠炎期间异常扩张的肠杆菌科细菌所占据的生态位，以促进益生菌定殖。此外，在结肠炎中高表达的钙结合蛋白钙卫蛋白可有效地从CTM中提取钙并释放钨，通过取代钼酶中的钼来抑制肠杆菌科细菌，而不影响递送的益生菌。此外，CTM对胃肠道（GI）的恶劣环境和肠道黏附具有抗性。因此，肠杆菌科细菌协同减少45倍，益生菌定殖增加25倍，从而对结肠炎产生显著的治疗效果，包括结肠长度的恢复、炎症反应的有效下调、受损黏膜屏障的恢复以及肠道微生物群稳态的恢复。
