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2322: The effects of fecal microbiota transplantation on the gut microbiota in subjects with Clostridium difficile infection

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 o...

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Autores principales: Elizabeth Langdon, Amy, Bulow, Christopher, Reske, Kim, Sun, Sherry, Hink, Tiffany, Jones, Courtney, Burnham, Carey-Ann D., Dubberke, Erik R., Dantas, Gautam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798968/
http://dx.doi.org/10.1017/cts.2017.130
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author Elizabeth Langdon, Amy
Bulow, Christopher
Reske, Kim
Sun, Sherry
Hink, Tiffany
Jones, Courtney
Burnham, Carey-Ann D.
Dubberke, Erik R.
Dantas, Gautam
author_facet Elizabeth Langdon, Amy
Bulow, Christopher
Reske, Kim
Sun, Sherry
Hink, Tiffany
Jones, Courtney
Burnham, Carey-Ann D.
Dubberke, Erik R.
Dantas, Gautam
author_sort Elizabeth Langdon, Amy
collection PubMed
description 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.
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spelling pubmed-67989682019-10-28 2322: The effects of fecal microbiota transplantation on the gut microbiota in subjects with Clostridium difficile infection Elizabeth Langdon, Amy Bulow, Christopher Reske, Kim Sun, Sherry Hink, Tiffany Jones, Courtney Burnham, Carey-Ann D. Dubberke, Erik R. Dantas, Gautam J Clin Transl Sci Clinical Trial 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. Cambridge University Press 2018-05-10 /pmc/articles/PMC6798968/ http://dx.doi.org/10.1017/cts.2017.130 Text en © The Association for Clinical and Translational Science 2018 http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Clinical Trial
Elizabeth Langdon, Amy
Bulow, Christopher
Reske, Kim
Sun, Sherry
Hink, Tiffany
Jones, Courtney
Burnham, Carey-Ann D.
Dubberke, Erik R.
Dantas, Gautam
2322: The effects of fecal microbiota transplantation on the gut microbiota in subjects with Clostridium difficile infection
title 2322: The effects of fecal microbiota transplantation on the gut microbiota in subjects with Clostridium difficile infection
title_full 2322: The effects of fecal microbiota transplantation on the gut microbiota in subjects with Clostridium difficile infection
title_fullStr 2322: The effects of fecal microbiota transplantation on the gut microbiota in subjects with Clostridium difficile infection
title_full_unstemmed 2322: The effects of fecal microbiota transplantation on the gut microbiota in subjects with Clostridium difficile infection
title_short 2322: The effects of fecal microbiota transplantation on the gut microbiota in subjects with Clostridium difficile infection
title_sort 2322: the effects of fecal microbiota transplantation on the gut microbiota in subjects with clostridium difficile infection
topic Clinical Trial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798968/
http://dx.doi.org/10.1017/cts.2017.130
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