Hou Weiliang, Cao Yuan, Wang Jifeng, Yin Fang, Wang Jiahui, Guo Ning, Wang Ziyi, Lv Xiaoqiong, Ma Chunlian, Chen Qiyi, Yang Rong, Wei Hong, Li Juanjuan, Wang Ruibing, Qin Huanlong
Research Institute of Intestinal Diseases, Shanghai Tenth People's Hospital Affiliated to Tongji University, 200072 Shanghai, China.
Department of Gastroenterology, Shanghai Institute of Pancreatic Diseases, Changhai Hospital; National Key Laboratory of Immunity and Inflammation, Naval Medical University, 200433 Shanghai, China.
Theranostics. 2025 Jan 6;15(5):2069-2084. doi: 10.7150/thno.104852. eCollection 2025.
Fecal microbiota transplantation (FMT) is advantageous for treating intractable diseases via the microbiota-gut-organ axis. However, invasive administration of gut microbiota via nasal feeding tubes limits the widespread application of FMT. Here, we attempted to develop a novel strategy to deliver gut microbiota using nanocapsules. Single-cell nanocapsules were fabricated within 1 h by layer-by-layer assembly of silk fibroin and phosphatidylcholine to generate a protective nanoshell on the cell surface of complicated microbiota. The physical properties of the microbiota nanocapsules were analyzed. The protective effects of nanocapsules on the gastrointestinal tract were analyzed both and . The efficacy of FMT assisted by single-cell nanocapsules (NanoFMT) was evaluated using the inflammatory response, gut microbiota balance, and histopathological analysis in animal model. The nanocapsules achieved a good coating ratio for a single type of microbe and complex microbiota, resulting in a remarkable increase in the survival rate of microbes in the gastrointestinal tract. NanoFMT improved the diversity and abundance of the gut microbiota better than common FMT in germ-free mice. Moreover, NanoFMT alleviated intestinal inflammation and positively reversed the microbiota balance in a mouse model of colitis compared with common FMT, assisted by the inherent anti-inflammatory effects of silk fibroin and phosphatidylcholine. Considering its rapid preparation, convenient delivery, and perfect therapeutic effect, we anticipate that NanoFMT may be a promising clinical candidate for next-generation FMT treatment.
粪便微生物群移植（FMT）通过微生物群-肠道-器官轴治疗难治性疾病具有优势。然而，通过鼻饲管侵入性地给予肠道微生物群限制了FMT的广泛应用。在此，我们试图开发一种使用纳米胶囊递送肠道微生物群的新策略。通过丝素蛋白和磷脂酰胆碱的逐层组装在1小时内制备单细胞纳米胶囊，以在复杂微生物群的细胞表面产生保护性纳米壳。分析了微生物群纳米胶囊的物理性质。从体内和体外两方面分析了纳米胶囊对胃肠道的保护作用。使用动物模型中的炎症反应、肠道微生物群平衡和组织病理学分析评估了单细胞纳米胶囊辅助的FMT（NanoFMT）的疗效。纳米胶囊对单一类型的微生物和复杂微生物群均实现了良好的包封率，从而显著提高了微生物在胃肠道中的存活率。在无菌小鼠中，NanoFMT比普通FMT更好地改善了肠道微生物群的多样性和丰度。此外，与普通FMT相比，在丝素蛋白和磷脂酰胆碱固有的抗炎作用辅助下，NanoFMT减轻了结肠炎小鼠模型中的肠道炎症，并积极逆转了微生物群平衡。考虑到其制备快速、递送方便且治疗效果理想，我们预计NanoFMT可能成为下一代FMT治疗的有前景的临床候选方法。
