Community dynamics drive punctuated engraftment of the fecal microbiome following transplantation using freeze-dried, encapsulated fecal microbiota

Christopher Staley, Byron P. Vaughn, Carolyn T. Graiziger, Stephanie Singroy, Matthew J. Hamilton, Dan Yao, Chi Chen, Alexander Khoruts, Michael J. Sadowsky

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Abstract

Fecal microbiota transplantation (FMT) is a highly effective treatment of recurrent and recalcitrant Clostridium difficile infection (rCDI). In a recent study oral-delivery of encapsulated, freeze-dried donor material, resulted in comparable rates of cure to colonoscopic approaches. Here we characterize shifts in the fecal bacterial community structure of patients treated for rCDI using encapsulated donor material. Prior to FMT, patient fecal samples showed declines in diversity and abundance of Firmicutes and Bacteroidetes, with concurrent increases in members of the Proteobacteria, specifically Enterobacteriaceae. Moreover, patients who experienced recurrence of CDI within the 2-month clinical follow-up had greater abundances of Enterobacteriaceae and did not show resolution of dysbioses. Despite resolution of rCDI following oral-administration of encapsulated fecal microbiota, community composition was slow to return to a normal donor-like assemblage. Post-FMT taxa within the Firmicutes showed rapid increases in relative abundance and did not vary significantly over time. Conversely, Bacteroidetes taxa only showed significant increases in abundance after one month post-FMT, corresponding to significant increases in the community attributable to the donors. Changes in the associations among dominant OTUs were observed at days, weeks, and months post-FMT, suggesting shifts in community dynamics may be related to the timing of increases in abundance of specific taxa. Administration of encapsulated, freeze-dried, fecal microbiota to rCDI patients resulted in restoration of bacterial diversity and resolution of dysbiosis. However, shifts in the fecal microbiome were incremental rather than immediate, and may be driven by changes in community dynamics reflecting changes in the host environment.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalGut Microbes
DOIs
StateAccepted/In press - Mar 9 2017

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Microbiota
Transplantation
Clostridium Infections
Clostridium difficile
Bacteroidetes
Enterobacteriaceae
Dysbiosis
Bacterial Structures
Proteobacteria
Oral Administration
Recurrence

Keywords

  • 16S rRNA
  • Capsule-delivered FMT
  • Clostridium difficile
  • cure
  • fecal microbial transplantation
  • microbial community structure
  • next-generation sequencing

ASJC Scopus subject areas

  • Microbiology
  • Gastroenterology
  • Microbiology (medical)
  • Infectious Diseases

MeSH PubMed subject areas

  • Journal Article

Cite this

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title = "Community dynamics drive punctuated engraftment of the fecal microbiome following transplantation using freeze-dried, encapsulated fecal microbiota",
abstract = "Fecal microbiota transplantation (FMT) is a highly effective treatment of recurrent and recalcitrant Clostridium difficile infection (rCDI). In a recent study oral-delivery of encapsulated, freeze-dried donor material, resulted in comparable rates of cure to colonoscopic approaches. Here we characterize shifts in the fecal bacterial community structure of patients treated for rCDI using encapsulated donor material. Prior to FMT, patient fecal samples showed declines in diversity and abundance of Firmicutes and Bacteroidetes, with concurrent increases in members of the Proteobacteria, specifically Enterobacteriaceae. Moreover, patients who experienced recurrence of CDI within the 2-month clinical follow-up had greater abundances of Enterobacteriaceae and did not show resolution of dysbioses. Despite resolution of rCDI following oral-administration of encapsulated fecal microbiota, community composition was slow to return to a normal donor-like assemblage. Post-FMT taxa within the Firmicutes showed rapid increases in relative abundance and did not vary significantly over time. Conversely, Bacteroidetes taxa only showed significant increases in abundance after one month post-FMT, corresponding to significant increases in the community attributable to the donors. Changes in the associations among dominant OTUs were observed at days, weeks, and months post-FMT, suggesting shifts in community dynamics may be related to the timing of increases in abundance of specific taxa. Administration of encapsulated, freeze-dried, fecal microbiota to rCDI patients resulted in restoration of bacterial diversity and resolution of dysbiosis. However, shifts in the fecal microbiome were incremental rather than immediate, and may be driven by changes in community dynamics reflecting changes in the host environment.",
keywords = "16S rRNA, Capsule-delivered FMT, Clostridium difficile, cure, fecal microbial transplantation, microbial community structure, next-generation sequencing",
author = "Christopher Staley and Vaughn, {Byron P.} and Graiziger, {Carolyn T.} and Stephanie Singroy and Hamilton, {Matthew J.} and Dan Yao and Chi Chen and Alexander Khoruts and Sadowsky, {Michael J.}",
year = "2017",
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AU - Hamilton,Matthew J.

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AU - Chen,Chi

AU - Khoruts,Alexander

AU - Sadowsky,Michael J.

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