Bacteria-based therapy has shown great promise in treating various diseases by regulating intestinal flora balance in pre-clinical and clinical studies. However, weak resistance against stress in the gastrointestinal (GI) tract and limited retention time in the intestine result in low bacteria availability and persistence, restricting further clinical application. Here, we report a double-layer coating strategy employing tannic acid (TA) and enteric L100 for probiotics encapsulation to address the delivery challenges after oral administration. The Escherichia coli Nissle 1917 (EcN) sequentially encapsulated by TA and L100 layers display robust resistances against the harsh external environment of the GI tract. Furthermore, the pH-responsive degradation of the outer L100 layer leads to the selective delivery of TA-EcN to the intestine, where the strong mucoadhesive capability of the TA layer prolongs the retention time of EcN without compromising the viability and proliferation capabilities of EcN, resulting in superior efficacy of prophylactic and treatment efficacy against colitis. To mitigate the potential side effects caused by long-term mucoadhesion of TA, the TA layer can be further removed by addition of ethylenediaminetetraacetic acid (EDTA). The spatiotemporal delivery of probiotics through double-layer encapsulation can augment the therapeutic efficacy of bacteria-based therapy against GI tract-related diseases.

基于细菌的疗法在临床前和临床研究中通过调节肠道菌群平衡在治疗各种疾病方面显示出巨大的希望。然而，胃肠道对压力的抵抗力较弱，在肠道中的停留时间有限，导致细菌可用性和持久性低，限制了进一步的临床应用。在这里，我们报告了一种采用单宁酸 (TA) 和肠溶性 L100 进行益生菌封装的双层包衣策略，以解决口服给药后的递送挑战。该大肠杆菌Nissle 1917 (EcN) 依次由 TA 和 L100 层封装，对胃肠道恶劣的外部环境显示出强大的抵抗力。此外，外层 L100 的 pH 响应性降解导致 TA-EcN 选择性递送到肠道，其中 TA 层强大的粘膜粘附能力延长了 EcN 的保留时间，而不会影响 EcN 的活力和增殖能力，从而对结肠炎具有优越的预防和治疗功效。为了减轻 TA 长期黏膜粘附引起的潜在副作用, 可以通过添加乙二胺四乙酸 (EDTA) 进一步去除 TA 层。