Community Assembly Following Fecal Microbiota Transplantation

Chris Smillie, Massachusetts Institute of Technology

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Fecal microbiota transplantation (FMT) is an emerging therapy for Clostridium difficile infections. However, although FMT is highly effective clinically, the ecological mechanisms that underlie it remain poorly understood. To investigate the community assembly dynamics in FMT recipients, we collected stool samples before and after therapy from 19 patients and four healthy donors. We used 16S amplicon sequencing and deep shotgun metagenomics to characterize 78 samples at an average depth of greater than 10 Gb per sample. We developed a method to statistically infer the frequencies and genotypes of bacterial strains across large metagenomics datasets, allowing us to map strain dynamics following FMT. We found that many donor strains consistently increase in abundance after transplantation, suggesting targets for isolation and characterization for future treatments involving synthetic communities. Moreover, we find consistent patterns of strain coexistence and competition across recipients treated by the same donor. FMT is associated with rapid, stable changes in both the strains that occupy a recipient’s microbiome as well as the composition of this bacterial community.

Abstract Author(s): C.S. Smillie, M.B. Smith, I. Youngster, C. Pindar, E. Hohmann, J. Sauk, D. Gevers, and E.J. Alm