Autologous fecal microbiota transplantation as a strategy to prevent colonization with multi-drug resistant organisms following antimicrobial therapy

Background: Although it is difficult to prevent infection with multidrug resistant organisms (MDROs), it may be possible to prevent fecal colonization and subsequent spread of MDROs. Our objective was to evaluate autologous transplantation of a healthy fecal microbiota (auto FMT) as a method to restore gut microbial diversity and prevent MDRO colonization following antimicrobial therapy.

Methods: Ten healthy subjects received five days of amoxicillin/clavulanate 875 mg BID. Half were randomized to auto FMT by enema and half to saline by enema. Stool was obtained prior to antibiotics, from the first bowel movement after the enema, and at days 7, 30, and 90 post-enema. Culturomics were applied to all stools and FMT products. This analysis will be complemented by 16S rRNA gene and shotgun sequencing. The Shannon diversity was calculated (H' = -Σ^R p_i ln p_i) for each sample based on culturomics.

Results: Culture results are available for four subjects; two received auto FMT and two saline. The investigators remain blinded to treatment and control groups.  The Shannon index over time (Figure 1) indicates that treatment with antibiotics did not significantly decrease microbial diversity in three of the four subjects (Post Abx time-point). Additionally, the species diversity in the FMT material for each subject was variable. In the case of subjects 3 and 4 it was markedly lower than their gut microbial diversity at enrollment.

Log scaled relative abundance was used as an additional measure of diversity in order to account for the possibility that small quantities of unique species are drivers of the robustness of gut microbial diversity. Species composition data (Figure 2) indicates that treatment with antibiotics did not affect diversity in three of four patients. Additionally, it appears that the loss of diversity in the FMT could be attributed to the loss of abundance of predominant species rather than due to the complete loss of species.

Conclusion: The effect of amoxicillin/clavulanate on the microbial diversity of the gut varies by subject. The preservation of species diversity in fecal samples prepared for transplantation is variable. Additional studies are needed to evaluate the impact of auto FMT on fecal flora following antimicrobial therapy.