Long-term changes of bacterial and viral compositions in the intestine of a recovered Clostridium difficile patient after fecal microbiota transplantation

  1. Karin Moelling1,2
  1. 1Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland;
  2. 2Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany;
  3. 3Institute of Food, Nutrition and Health, ETH Zurich, 8096 Zurich, Switzerland;
  4. 4Functional Genomics Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland;
  5. 5Division of Gastroenterology and Hepatology, University Hospital Zurich, 8006 Zurich, Switzerland;
  1. Corresponding authors: moelling{at}molgen.mpg.de, felixbroecker{at}gmx.net
  1. 7 These authors contributed equally to this work.

  • 6 Present address: Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.

Abstract

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infections (RCDIs). However, long-term effects on the patients’ gut microbiota and the role of viruses remain to be elucidated. Here, we characterized bacterial and viral microbiota in the feces of a cured RCDI patient at various time points until 4.5 yr post-FMT compared with the stool donor. Feces were subjected to DNA sequencing to characterize bacteria and double-stranded DNA (dsDNA) viruses including phages. The patient's microbial communities varied over time and showed little overall similarity to the donor until 7 mo post-FMT, indicating ongoing gut microbiota adaption in this time period. After 4.5 yr, the patient's bacteria attained donor-like compositions at phylum, class, and order levels with similar bacterial diversity. Differences in the bacterial communities between donor and patient after 4.5 yr were seen at lower taxonomic levels. C. difficile remained undetectable throughout the entire timespan. This demonstrated sustainable donor feces engraftment and verified long-term therapeutic success of FMT on the molecular level. Full engraftment apparently required longer than previously acknowledged, suggesting the implementation of year-long patient follow-up periods into clinical practice. The identified dsDNA viruses were mainly Caudovirales phages. Unexpectedly, sequences related to giant algae–infecting Chlorella viruses were also detected. Our findings indicate that intestinal viruses may be implicated in the establishment of gut microbiota. Therefore, virome analyses should be included in gut microbiota studies to determine the roles of phages and other viruses—such as Chlorella viruses—in human health and disease, particularly during RCDI.

  • Received May 20, 2015.
  • Accepted August 27, 2015.

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