BioTechnology Institute, University of Minnesota, St. Paul, MN, USA.
Department of Soil, Water, and Climate, Department of Plant and Microbial Biology, University of Minnesota, St. Paul, MN, USA.
Dig Dis Sci. 2024 May;69(5):1778-1784. doi: 10.1007/s10620-024-08351-7. Epub 2024 Mar 8.
Fecal microbiota transplants can be administered orally in encapsulated form or require invasive procedures to administer liquid formulations. There is a need for an oral liquid formulation of fecal microbiota for patients who are unable to swallow capsules, especially if they require multiple, repeated administrations.
These studies were conducted to develop a protocol to manufacture an organoleptically acceptable powdered fecal microbiota formulation that can be suspended in a liquid carrier and used for fecal microbiota transplantation.
Several processing steps were investigated, including extra washes of microbiota prior to lyophilization and an addition of a flavoring agent. The viability of bacteria in the transplant formulation was tested using live/dead microscopy staining and engraftment into antibiotic-treated mice. After development of a clinical protocol for suspension of the powdered microbiota, the new formulation was tested in three elderly patients with recurrent Clostridioides difficile infections and who have difficulties in swallowing capsules. Changes in the microbial community structure in one of the patients were characterized using 16S rRNA gene profiling and engraftment analysis.
The processing steps used to produce an organoleptically acceptable suspension of powdered fecal microbiota did not result in loss of its viability. The powder could be easily suspended in a liquid carrier. The use of the new formulation was associated with abrogation of the cycle of C. difficile infection recurrences in the three patients.
We developed a novel organoleptically acceptable liquid formulation of fecal microbiota that is suitable for use in clinical trials for patients with difficulties in swallowing capsules.
粪便微生物群移植可以口服封装形式进行，也可以通过侵入性程序来施用液体制剂。对于不能吞咽胶囊的患者，尤其是需要多次重复给药的患者，需要一种口服液体粪便微生物群制剂。
这些研究旨在制定一项方案，以制造一种感官可接受的粉状粪便微生物群制剂，该制剂可悬浮在液体载体中，并用于粪便微生物群移植。
研究了几个处理步骤，包括在冻干前对微生物群进行多次额外洗涤，并添加调味剂。使用活/死显微镜染色和抗生素处理的小鼠植入来测试移植制剂中细菌的活力。在开发了用于混悬粉状微生物群的临床方案后，该新制剂在 3 名患有复发性艰难梭菌感染且吞咽胶囊有困难的老年患者中进行了测试。使用 16S rRNA 基因谱和植入分析对其中一名患者的微生物群落结构变化进行了表征。
用于生产感官可接受的粉状粪便微生物群混悬液的处理步骤不会导致其活力丧失。粉末可以很容易地悬浮在液体载体中。新制剂的使用与 3 名患者艰难梭菌感染复发周期的终止相关。
我们开发了一种新型感官可接受的粪便微生物群液体制剂，适用于吞咽胶囊有困难的患者的临床试验。
