Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study.

ABSTRACT

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 × 1011 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.