TY - JOUR
T1 - Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study
AU - Staley, Christopher
AU - Hamilton, Matthew J.
AU - Vaughn, Byron P.
AU - Graiziger, Carolyn T.
AU - Newman, Krista M.
AU - Kabage, Amanda J.
AU - Sadowsky, Michael J.
AU - Khoruts, Alexander
N1 - Publisher Copyright:
© 2017 by the American College of Gastroenterology.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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.
AB - 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.
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U2 - 10.1038/ajg.2017.6
DO - 10.1038/ajg.2017.6
M3 - Article
C2 - 28195180
AN - SCOPUS:85012894735
SN - 0002-9270
VL - 112
SP - 940
EP - 947
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
IS - 6
ER -