Cargando…

Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen

The gut microbiota has emerged as a key mediator of human physiology, and germ-free mice have been essential in demonstrating a role for the microbiome in disease. Preclinical models using conventional mice offer the advantage of working with a mature immune system. However, optimal protocols for fe...

Descripción completa

Detalles Bibliográficos
Autores principales: Gopalakrishnan, Vancheswaran, Dozier, Elizabeth Ashley, Glover, Matthew S., Novick, Steven, Ford, Michael, Morehouse, Christopher, Warrener, Paul, Caceres, Carolina, Hess, Sonja, Sellman, Bret R., Cohen, Taylor S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306289/
https://www.ncbi.nlm.nih.gov/pubmed/34209573
http://dx.doi.org/10.3390/microorganisms9071399
_version_ 1783727773165027328
author Gopalakrishnan, Vancheswaran
Dozier, Elizabeth Ashley
Glover, Matthew S.
Novick, Steven
Ford, Michael
Morehouse, Christopher
Warrener, Paul
Caceres, Carolina
Hess, Sonja
Sellman, Bret R.
Cohen, Taylor S.
author_facet Gopalakrishnan, Vancheswaran
Dozier, Elizabeth Ashley
Glover, Matthew S.
Novick, Steven
Ford, Michael
Morehouse, Christopher
Warrener, Paul
Caceres, Carolina
Hess, Sonja
Sellman, Bret R.
Cohen, Taylor S.
author_sort Gopalakrishnan, Vancheswaran
collection PubMed
description The gut microbiota has emerged as a key mediator of human physiology, and germ-free mice have been essential in demonstrating a role for the microbiome in disease. Preclinical models using conventional mice offer the advantage of working with a mature immune system. However, optimal protocols for fecal microbiota transplant (FMT) engraftment in conventional mice are yet to be established. Conventional BALB/c mice were randomized to receive 3-day (3d) or 3-week (3w) antibiotic (ABX) regimen in their drinking water followed by 1 or 5-daily FMTs from a human donor. Fecal samples were collected longitudinally and characterized using 16S ribosomal RNA (rRNA) sequencing. Semi-targeted metabolomic profiling of fecal samples was also done with liquid chromatography–mass spectrometry (LC-MS). Lastly, we sought to confirm our findings in BKS mice. Recovery of baseline diversity scores were greatest in the 3d groups, driven by re-emergence of mouse commensal microbiota, whereas the most resemblance to donor microbiota was seen in the 3w + 5-FMT group. Amplicon sequence variants (ASVs) that were linked to the input material (human ASVs) engrafted to a significantly greater extent when compared to mouse ASVs in the 3-week groups but not the 3-day groups. Lastly, comparison of metabolomic profiles revealed distinct functional profiles by ABX regimen. These results indicate successful model optimization and emphasize the importance of ABX duration and frequency of FMT dosing; the most stable and reliable colonization by donor ASVs was seen in the 3wk + 5-FMT group.
format Online
Article
Text
id pubmed-8306289
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83062892021-07-25 Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen Gopalakrishnan, Vancheswaran Dozier, Elizabeth Ashley Glover, Matthew S. Novick, Steven Ford, Michael Morehouse, Christopher Warrener, Paul Caceres, Carolina Hess, Sonja Sellman, Bret R. Cohen, Taylor S. Microorganisms Article The gut microbiota has emerged as a key mediator of human physiology, and germ-free mice have been essential in demonstrating a role for the microbiome in disease. Preclinical models using conventional mice offer the advantage of working with a mature immune system. However, optimal protocols for fecal microbiota transplant (FMT) engraftment in conventional mice are yet to be established. Conventional BALB/c mice were randomized to receive 3-day (3d) or 3-week (3w) antibiotic (ABX) regimen in their drinking water followed by 1 or 5-daily FMTs from a human donor. Fecal samples were collected longitudinally and characterized using 16S ribosomal RNA (rRNA) sequencing. Semi-targeted metabolomic profiling of fecal samples was also done with liquid chromatography–mass spectrometry (LC-MS). Lastly, we sought to confirm our findings in BKS mice. Recovery of baseline diversity scores were greatest in the 3d groups, driven by re-emergence of mouse commensal microbiota, whereas the most resemblance to donor microbiota was seen in the 3w + 5-FMT group. Amplicon sequence variants (ASVs) that were linked to the input material (human ASVs) engrafted to a significantly greater extent when compared to mouse ASVs in the 3-week groups but not the 3-day groups. Lastly, comparison of metabolomic profiles revealed distinct functional profiles by ABX regimen. These results indicate successful model optimization and emphasize the importance of ABX duration and frequency of FMT dosing; the most stable and reliable colonization by donor ASVs was seen in the 3wk + 5-FMT group. MDPI 2021-06-29 /pmc/articles/PMC8306289/ /pubmed/34209573 http://dx.doi.org/10.3390/microorganisms9071399 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gopalakrishnan, Vancheswaran
Dozier, Elizabeth Ashley
Glover, Matthew S.
Novick, Steven
Ford, Michael
Morehouse, Christopher
Warrener, Paul
Caceres, Carolina
Hess, Sonja
Sellman, Bret R.
Cohen, Taylor S.
Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen
title Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen
title_full Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen
title_fullStr Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen
title_full_unstemmed Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen
title_short Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen
title_sort engraftment of bacteria after fecal microbiota transplantation is dependent on both frequency of dosing and duration of preparative antibiotic regimen
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306289/
https://www.ncbi.nlm.nih.gov/pubmed/34209573
http://dx.doi.org/10.3390/microorganisms9071399
work_keys_str_mv AT gopalakrishnanvancheswaran engraftmentofbacteriaafterfecalmicrobiotatransplantationisdependentonbothfrequencyofdosinganddurationofpreparativeantibioticregimen
AT dozierelizabethashley engraftmentofbacteriaafterfecalmicrobiotatransplantationisdependentonbothfrequencyofdosinganddurationofpreparativeantibioticregimen
AT glovermatthews engraftmentofbacteriaafterfecalmicrobiotatransplantationisdependentonbothfrequencyofdosinganddurationofpreparativeantibioticregimen
AT novicksteven engraftmentofbacteriaafterfecalmicrobiotatransplantationisdependentonbothfrequencyofdosinganddurationofpreparativeantibioticregimen
AT fordmichael engraftmentofbacteriaafterfecalmicrobiotatransplantationisdependentonbothfrequencyofdosinganddurationofpreparativeantibioticregimen
AT morehousechristopher engraftmentofbacteriaafterfecalmicrobiotatransplantationisdependentonbothfrequencyofdosinganddurationofpreparativeantibioticregimen
AT warrenerpaul engraftmentofbacteriaafterfecalmicrobiotatransplantationisdependentonbothfrequencyofdosinganddurationofpreparativeantibioticregimen
AT cacerescarolina engraftmentofbacteriaafterfecalmicrobiotatransplantationisdependentonbothfrequencyofdosinganddurationofpreparativeantibioticregimen
AT hesssonja engraftmentofbacteriaafterfecalmicrobiotatransplantationisdependentonbothfrequencyofdosinganddurationofpreparativeantibioticregimen
AT sellmanbretr engraftmentofbacteriaafterfecalmicrobiotatransplantationisdependentonbothfrequencyofdosinganddurationofpreparativeantibioticregimen
AT cohentaylors engraftmentofbacteriaafterfecalmicrobiotatransplantationisdependentonbothfrequencyofdosinganddurationofpreparativeantibioticregimen