Time series strain tracking analysis post fecal transplantation identifies individual specific patterns of fecal dominant donor, recipient, and unrelated microbial strains

Abstract

Background Fecal microbial transplantation (FMT) has been used with the therapeutic intent to change the functions of the gut microbial community in metabolism and host immunity. For most of these therapies, the recipients are not given antibiotics to eliminate the microbial community prior to transplant with donor fecal microbes resulting in the initial gut microbial community following FMT consisting of a consortium of donor and recipient microbes. The detailed analysis of the fecal samples from these FMT over time provides a unique opportunity to study the changes in the gut microbial strain community that occurs following the introduction of new microbial strains (donor) into an established community (recipient). Methods In this study, we have metagenomic data set consisting of 5 FMT that contained donor, recipient and recipient post FMT taken multiple times for periods up to 535 days after the FMT. We used two established strain tracking methods, Window-based Single Nucleotide Variant (SNV) Similarity (WSS) and StrainPhlAn, to determine the presence of donor and recipient microbial strains following FMT. To assess recombination between donor and recipient strains of Bacteroides vulgatus post FMT, we used BLAST+ to analyze the data sets for Bacteroidales -specific antimicrobial proteins (BSAP-3) that have known functions to restrict species specific replication. Results We found that Alistipes onderdonkii , Alistipes shahii , Alistipes putredinis , and Parabacteroides merdae , all had patterns post FMT consisting of either dominant donor or recipient microbial strains in the feces. In contrast, the analysis of Bacteroides spp . in five FMT pairs revealed inter-individual oscillation over time with the appearance of either donor or recipient fecal strain dominance. In some instances, B . vulgatus and B . uniformis were also identified after FMT that were not related to either the donor or recipient. Finally, in one of the FMT, we identified a distinct B . vulgatus strain post-FMT that matched the pre-FMT strain but was BSAP-3 positive, suggesting a possible recombination event between the donor and recipient strains. Conclusion The complex oscillating patterns of the appearance of fecal dominant donor, recipient or unrelated strains following extended times post FMT provide new insights into the dynamics of the microbial community interactions with the recipients following FMT. The result from our analysis has implications for the use of FMT to predictably change the biological functions of the gut community in metabolism and host immunity.

Bacteroidales-Specific Antimicrobial Genes Can Influence the Selection of the Dominant Fecal Strain of Bacteroides vulgatus and Bacteroides uniformis from the Gastrointestinal Tract Microbial Community

“…Since the human microbiome is recognized as being diverse and generally individual specific, a strength of our study was the use of three longitudinal data sets that allowed the comparison of samples from the same individual pre and post treatment. Additional follow up studies with clinical implications would include an analysis of patients pre and post fecal transplant and those individuals that have had perturbation of their GIT ecosystem from oral drugs [37][38][39].…”