Strain Tracking Reveals the Determinants of Bacterial Engraftment in the Human Gut Following Fecal Microbiota Transplantation

Christopher S. Smillie, Jenny Sauk, Dirk Gevers, Jonathan Friedman, Jaeyun Sung, Ilan Youngster, Elizabeth L. Hohmann, Christopher Staley, Alexander Khoruts, Michael J. Sadowsky, Jessica R. Allegretti, Mark B. Smith, Ramnik J. Xavier, Eric J. Alm

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Fecal microbiota transplantation (FMT) from healthy donor to patient is a treatment for microbiome-associated diseases. Although the success of FMT requires donor bacteria to engraft in the patient's gut, the forces governing engraftment in humans are unknown. Here we use an ongoing clinical experiment, the treatment of recurrent Clostridium difficile infection, to uncover the rules of engraftment in humans. We built a statistical model that predicts which bacterial species will engraft in a given host, and developed Strain Finder, a method to infer strain genotypes and track them over time. We find that engraftment can be predicted largely from the abundance and phylogeny of bacteria in the donor and the pre-FMT patient. Furthermore, donor strains within a species engraft in an all-or-nothing manner and previously undetected strains frequently colonize patients receiving FMT. We validated these findings for metabolic syndrome, suggesting that the same principles of engraftment extend to other indications. Smillie et al. profile the gut microbiota of recurrent Clostridium difficile patients during fecal microbiota transplantation (FMT) and uncover the principles of microbiota engraftment in humans. They validate their findings across several FMT datasets and in another disease context, metabolic syndrome.

Original languageEnglish (US)
Pages (from-to)229-240.e5
JournalCell Host and Microbe
Volume23
Issue number2
DOIs
StatePublished - Feb 14 2018

Keywords

  • C. difficile
  • Clostridium difficile
  • FMT
  • bacterial engraftment
  • fecal microbiota transplant
  • fecal transplant
  • human microbiome
  • human microbiota
  • strain inference
  • strain tracking

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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