Background

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.

Aims

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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使用新型、可饮用、口服粪便微生物制剂成功治疗复发性艰难梭菌感染

背景

粪便微生物群移植可以以胶囊形式口服施用，或者需要侵入性操作来施用液体制剂。对于无法吞咽胶囊的患者，尤其是需要多次重复给药的患者，需要一种粪便微生物群的口服液体制剂。

目标

进行这些研究是为了开发一种方案来制造感官上可接受的粉末状粪便微生物群制剂，该制剂可以悬浮在液体载体中并用于粪便微生物群移植。

方法

研究了几个加工步骤，包括冻干前额外洗涤微生物群和添加调味剂。使用活/死显微镜染色和植入抗生素治疗的小鼠中来测试移植制剂中细菌的活力。在制定了悬浮粉末微生物群的临床方案后，新配方在三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 基因分析和植入分析来表征其中一名患者微生物群落结构的变化。

结果

用于生产感官上可接受的粉末状粪便微生物悬浮液的加工步骤并未导致其活力丧失。该粉末可以很容易地悬浮在液体载体中。新制剂的使用与三名患者艰难梭菌感染复发周期的消除相关。

结论

我们开发了一种新型的感官上可接受的粪便微生物液体制剂，适用于吞咽胶囊困难患者的临床试验。