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The effects of fecal microbiota transplantation on the gut microbiota in subjects with Clostridium difficile infection

Published online by Cambridge University Press:  10 May 2018

Christopher Bulow
Affiliation:
Washington University School of Medicine, St. Louis, MO, USA;
Kim Reske
Affiliation:
Barnes Jewish Hospital, St. Louis, MO, USA;
Sherry Sun
Affiliation:
Washington University School of Medicine, St. Louis, MO, USA;
Tiffany Hink
Affiliation:
Barnes Jewish Hospital, St. Louis, MO, USA;
Courtney Jones
Affiliation:
Rebiotix, Inc., Minneapolis, MN, USA
Carey-Ann D. Burnham
Affiliation:
Washington University School of Medicine, St. Louis, MO, USA; Barnes Jewish Hospital, St. Louis, MO, USA;
Erik R. Dubberke
Affiliation:
Barnes Jewish Hospital, St. Louis, MO, USA;
Gautam Dantas
Affiliation:
Washington University School of Medicine, St. Louis, MO, USA;
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Abstract

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OBJECTIVES/SPECIFIC AIMS: Clostridium difficile is the most common cause of infectious antibiotic associated diarrhea. It is often refractory to antimicrobial therapy and fecal microbiota transplantation (FMT) is emerging as a therapeutic option. The objective is to characterize the direct effects of FMT on the gut microbiota. METHODS/STUDY POPULATION: Fecal specimens were obtained from a cohort of 29 subjects with recurrent C. difficile infection who received FMTs from 1 of 4 healthy donors as part of a phase 2 trial (Rebiotix). Fecal specimens were collected from the subject before FMT and up to 6 months post FMT. 16S rRNA sequencing and whole-genome shotgun sequencing were used to assess microbial community composition as compared by weighted Unifrac. RESULTS/ANTICIPATED RESULTS: Before treatment, the microbial community of subjects with C. difficile infection was highly distinct from the composition of the healthy donors in terms of metabolic profile. Quantification of phylogenetic community distance from donor by weighted Unifrac distance showed a significant decrease within the 1st week (Wilcoxon rank sum, p<0.01). This metric was predictive of both treatment failures and antibiotic resistance gene count (LR=22.45, p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: We conclude that distance from donor is a useful metric to quantify FMT success and that FMTs are a promising treatment for otherwise untreatable carriage of antibiotic resistance genes and organisms.

Type
Clinical Trial
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Association for Clinical and Translational Science 2018