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

doi:10.1016/j.chom.2018.01.003

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

Cell Host Microbe. 2018 Feb 14;23(2):229-240.e5. doi: 10.1016/j.chom.2018.01.003.

Authors

Affiliations

¹ Broad Institute of MIT and Harvard, Cambridge, MA, USA; Computational and Systems Biology, MIT, Cambridge, MA, USA; The Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA, USA.
² Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
³ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴ Department of Physics, MIT, Cambridge, MA, USA.
⁵ Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
⁷ Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
⁸ BioTechnology Institute, University of Minnesota, St. Paul, MN, USA.
⁹ BioTechnology Institute, University of Minnesota, St. Paul, MN, USA; Division of Gastroenterology, University of Minnesota, St. Paul, MN, USA; Center for Immunology, University of Minnesota, St. Paul, MA, USA.
¹⁰ Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Boston, MA, USA.
¹¹ The Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA, USA; Finch Therapeutics, Somerville, MA, USA.
¹² Broad Institute of MIT and Harvard, Cambridge, MA, USA; The Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: xavier@molbio.mgh.harvard.edu.
¹³ Broad Institute of MIT and Harvard, Cambridge, MA, USA; The Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA, USA; Finch Therapeutics, Somerville, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA. Electronic address: ejalm@mit.edu.

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.

Keywords: C. difficile; Clostridium difficile; FMT; bacterial engraftment; fecal microbiota transplant; fecal transplant; human microbiome; human microbiota; strain inference; strain tracking.

MeSH terms

Biodiversity
Clostridioides difficile / growth & development*
Clostridium Infections / prevention & control*
Clostridium Infections / therapy
Fecal Microbiota Transplantation / methods*
Gastrointestinal Microbiome / physiology*
Gastrointestinal Tract / microbiology*
Humans
Models, Biological
Recurrence
Secondary Prevention / methods*

Abstract

MeSH terms

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