Microbial Strain Engraftment, Persistence and Replacement after Fecal Microbiota Transplantation

Summary Fecal Microbiota Transplantation (FMT) has been clinically validated as a treatment for recurrent Clostridioides difficile infection (rCDI) and associated with the compositional and functional restoration of the patient gut microbiota. To characterize the underlying microbiota dynamics of patient and donor strain engraftment, persistence and replacement during FMT, we combined new and existing metagenomic sequence data and developed the bioinformatic SameStr program for the species-specific detection of shared subspecies lineages, including non-dominant strains. We show that personal gut strain profiles are identifiable and detect engraftment after successful and failed FMT in rCDI recipients, specifically of those donor strains that are abundant and stable in healthy individuals. We identify microbiota parameters in statistical models to predict donor species and strain engraftment, as well as recipient strain persistence and replacement. Our findings raise concerns over FMT consequences from questionable donors and suggest that personalized FMT strategies are feasible for targeted microbiota modulation.