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Successful Bacterial Engraftment Identified by Next-Generation Sequencing Predicts Success of Fecal Microbiota Transplant for Clostridioides difficile

BACKGROUND: The effectiveness of fecal microbiota transplantation (FMT), a treatment for Clostridioides difficile infection (CDI), is dependent on successful engraftment (incorporation) of donor stool. We present a method for evaluating engraftment success based on next-generation sequencing (NGS)-b...

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Autores principales: Hazan, Sabine, Dave, Sonya, Papoutsis, Andreas J., Barrows, Brad D., Borody, Thomas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elmer Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577596/
https://www.ncbi.nlm.nih.gov/pubmed/34804275
http://dx.doi.org/10.14740/gr1434
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author Hazan, Sabine
Dave, Sonya
Papoutsis, Andreas J.
Barrows, Brad D.
Borody, Thomas J.
author_facet Hazan, Sabine
Dave, Sonya
Papoutsis, Andreas J.
Barrows, Brad D.
Borody, Thomas J.
author_sort Hazan, Sabine
collection PubMed
description BACKGROUND: The effectiveness of fecal microbiota transplantation (FMT), a treatment for Clostridioides difficile infection (CDI), is dependent on successful engraftment (incorporation) of donor stool. We present a method for evaluating engraftment success based on next-generation sequencing (NGS)-based profiling of bacterial strains present in donor and recipient stool, and we suggest its potential to guide treatment decisions. METHODS: Bacterial strains in stool samples from three patients from the clinic and one donor were analyzed via NGS and metagenomic sequencing, before and 1 month after FMT for CDI. The similarity of strains present was assessed via relative abundance, principal component analysis, Shannon and Simpson diversity indexes, and Bray-Curtis dissimilarity matrix. A positive outcome was successful engraftment, where the post-FMT sample closely resembled that of the donor and CDI was cured. RESULTS: Patients (Pts.) 1 and 2, but not Pt. 3’s stool samples closely resembled the donor specimen post-FMT. Noteworthy, Pt. 3 pre-FMT sample was less similar to the donor than that of Pts. 1 and 2. All methods of assessing similarity and dissimilarity used yielded virtually identical conclusions. Pts. 1 and 2 which closely resembled donor specimen, eradicated CDI giving a surrogate objective measure of engraftment. CONCLUSIONS: Success of engraftment in FMT can be assessed using NGS and metagenomic analysis and parallels success in curing CDI of the microbiome. The statistical methods we present here are reliable and consistent for such purposes. The dissimilarity of Pt. 3 to the donor combined with the failure of engraftment and failure to cure CDI in Pt. 3 suggests that FMT success may be predictable by comparing pre-FMT samples to donor. There is no clinical trial registry listing this study.
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spelling pubmed-85775962021-11-18 Successful Bacterial Engraftment Identified by Next-Generation Sequencing Predicts Success of Fecal Microbiota Transplant for Clostridioides difficile Hazan, Sabine Dave, Sonya Papoutsis, Andreas J. Barrows, Brad D. Borody, Thomas J. Gastroenterology Res Short Communication BACKGROUND: The effectiveness of fecal microbiota transplantation (FMT), a treatment for Clostridioides difficile infection (CDI), is dependent on successful engraftment (incorporation) of donor stool. We present a method for evaluating engraftment success based on next-generation sequencing (NGS)-based profiling of bacterial strains present in donor and recipient stool, and we suggest its potential to guide treatment decisions. METHODS: Bacterial strains in stool samples from three patients from the clinic and one donor were analyzed via NGS and metagenomic sequencing, before and 1 month after FMT for CDI. The similarity of strains present was assessed via relative abundance, principal component analysis, Shannon and Simpson diversity indexes, and Bray-Curtis dissimilarity matrix. A positive outcome was successful engraftment, where the post-FMT sample closely resembled that of the donor and CDI was cured. RESULTS: Patients (Pts.) 1 and 2, but not Pt. 3’s stool samples closely resembled the donor specimen post-FMT. Noteworthy, Pt. 3 pre-FMT sample was less similar to the donor than that of Pts. 1 and 2. All methods of assessing similarity and dissimilarity used yielded virtually identical conclusions. Pts. 1 and 2 which closely resembled donor specimen, eradicated CDI giving a surrogate objective measure of engraftment. CONCLUSIONS: Success of engraftment in FMT can be assessed using NGS and metagenomic analysis and parallels success in curing CDI of the microbiome. The statistical methods we present here are reliable and consistent for such purposes. The dissimilarity of Pt. 3 to the donor combined with the failure of engraftment and failure to cure CDI in Pt. 3 suggests that FMT success may be predictable by comparing pre-FMT samples to donor. There is no clinical trial registry listing this study. Elmer Press 2021-10 2021-10-14 /pmc/articles/PMC8577596/ /pubmed/34804275 http://dx.doi.org/10.14740/gr1434 Text en Copyright 2021, Hazan et al. https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Hazan, Sabine
Dave, Sonya
Papoutsis, Andreas J.
Barrows, Brad D.
Borody, Thomas J.
Successful Bacterial Engraftment Identified by Next-Generation Sequencing Predicts Success of Fecal Microbiota Transplant for Clostridioides difficile
title Successful Bacterial Engraftment Identified by Next-Generation Sequencing Predicts Success of Fecal Microbiota Transplant for Clostridioides difficile
title_full Successful Bacterial Engraftment Identified by Next-Generation Sequencing Predicts Success of Fecal Microbiota Transplant for Clostridioides difficile
title_fullStr Successful Bacterial Engraftment Identified by Next-Generation Sequencing Predicts Success of Fecal Microbiota Transplant for Clostridioides difficile
title_full_unstemmed Successful Bacterial Engraftment Identified by Next-Generation Sequencing Predicts Success of Fecal Microbiota Transplant for Clostridioides difficile
title_short Successful Bacterial Engraftment Identified by Next-Generation Sequencing Predicts Success of Fecal Microbiota Transplant for Clostridioides difficile
title_sort successful bacterial engraftment identified by next-generation sequencing predicts success of fecal microbiota transplant for clostridioides difficile
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577596/
https://www.ncbi.nlm.nih.gov/pubmed/34804275
http://dx.doi.org/10.14740/gr1434
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