OBJECTIVES:Fecal microbiota transplantation (FMT) is increasingly being used for treatment of recurrent Clostridium difficile infection (R-CDI) that cannot be cured with antibiotics alone. In addition, FMT is being investigated for a variety of indications where restoration or restructuring of the gut microbial community is hypothesized to be beneficial. We sought to develop a stable, freeze-dried encapsulated preparation of standardized fecal microbiota that can be used for FMT with ease and convenience in clinical practice and research.METHODS:We systematically developed a lyophilization protocol that preserved the viability of bacteria across the taxonomic spectrum found in fecal microbiota and yielded physicochemical properties that enabled consistent encapsulation. We also treated a cohort of R-CDI patients with a range of doses of encapsulated microbiota and analyzed the associated changes in the fecal microbiome of the recipients.RESULTS:The optimized lyophilized preparation satisfied all our preset goals for physicochemical properties, encapsulation ease, stability at different temperatures, and microbiota viability in vitro and in vivo (germ-free mice). The capsule treatment was administered to 49 patients. Overall, 43/49 (88%) of patients achieved a clinical success, defined as no recurrence of CDI over 2 months. Analysis of the fecal microbiome demonstrated near normalization of the fecal microbial community by 1 month following FMT treatment. The simplest protocol using the lowest dose (2.1-2.5 × 10 11 bacteria in 2-3 capsules) without any colon purgative performed equally well in terms of clinical outcomes and microbiota engraftment.CONCLUSIONS:A single administration of encapsulated, freeze-dried fecal microbiota from a healthy donor was highly successful in treating antibiotic-refractory R-CDI syndrome.
Bibliographical noteFunding Information:
The study was supported by grants from the NIH 1R21-AI114722-01 (AK, MJS) to analyze the bacterial composition of the fecal samples, CIPAC Limited (AK, MJS) to test various parameters for optimization of microbiota preparation. Additional support for capsule preparation and collection biological specimens was provided by the philanthropic support of Achieving Cures Together, Ms. Emily Haller, and the Hubbard Foundation. None of the sponsors had any roles (other than funding) in the study design, collection, analysis, interpretation of data, or writing of the manuscript.
© 2017 by the American College of Gastroenterology.
Copyright 2017 Elsevier B.V., All rights reserved.