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

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. [Display omitted] •Gut microbiota of 18 C. difficile patients profiled during fecal transplantation•Developed Strain Finder, a method to infer strain genotypes and track them over time•Bacterial abundance and phylogeny are the strongest determinants of engraftment•Unlike bacterial species, closely related strains engraft in an all-or-nothing pattern 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.