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Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile

BACKGROUND: Fecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient’s gut commensal microbiota, we have analyzed the colonization potential of the d...

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Autores principales: Kumar, Ranjit, Maynard, Craig L., Eipers, Peter, Goldsmith, Kelly T., Ptacek, Travis, Grubbs, J. Aaron, Dixon, Paula, Howard, Donna, Crossman, David K., Crowley, Michael R., Benjamin, William H., Lefkowitz, Elliot J., Weaver, Casey T., Rodriguez, J. Martin, Morrow, Casey D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711103/
https://www.ncbi.nlm.nih.gov/pubmed/26758906
http://dx.doi.org/10.1186/s12866-015-0622-2
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author Kumar, Ranjit
Maynard, Craig L.
Eipers, Peter
Goldsmith, Kelly T.
Ptacek, Travis
Grubbs, J. Aaron
Dixon, Paula
Howard, Donna
Crossman, David K.
Crowley, Michael R.
Benjamin, William H.
Lefkowitz, Elliot J.
Weaver, Casey T.
Rodriguez, J. Martin
Morrow, Casey D.
author_facet Kumar, Ranjit
Maynard, Craig L.
Eipers, Peter
Goldsmith, Kelly T.
Ptacek, Travis
Grubbs, J. Aaron
Dixon, Paula
Howard, Donna
Crossman, David K.
Crowley, Michael R.
Benjamin, William H.
Lefkowitz, Elliot J.
Weaver, Casey T.
Rodriguez, J. Martin
Morrow, Casey D.
author_sort Kumar, Ranjit
collection PubMed
description BACKGROUND: Fecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient’s gut commensal microbiota, we have analyzed the colonization potential of the donor, recipient and recipient post transplant fecal samples using transplantation in gnotobiotic mice. RESULTS: A total of nine samples from three human donors, recipient’s pre and post FMT were transplanted into gnotobiotic mice. Microbiome analysis of three donor fecal samples revealed the presence of a high relative abundance of commensal microbes from the family Bacteriodaceae and Lachnospiraceae that were almost absent in the three recipient pre FMT fecal samples (<0.01 %). The microbe composition in gnotobiotic mice transplanted with the donor fecal samples was similar to the human samples. The recipient samples contained Enterobacteriaceae, Lactobacillaceae, Enterococcaceae in relative abundance of 43, 11, 8 %, respectively. However, gnotobiotic mice transplanted with the recipient fecal samples had an average relative abundance of unclassified Clostridiales of 55 %, approximately 7000 times the abundance in the recipient fecal samples prior to transplant. Microbiome analysis of fecal samples from the three patients early (2–4 weeks) after FMT revealed a microbe composition with the relative abundance of both Bacteriodaceae and Lachnospiraceae that was approximately 7 % of that of the donor. In contrast, gnotobioitc mice transplanted with the fecal samples obtained from the three at early times post FMT revealed increases in the relative abundance of Bacteriodaceae and Lachnospiraceae microbe compositions to levels similar to the donor fecal samples. Furthermore, the unclassified Clostridiales in the recipient samples post FMT was reduced to an average of 10 %. CONCLUSION: We have used transplantation into gnotobiotic mice to evaluate the colonization potential of microbiota in FMT patients early after transplant. The commensal microbes present at early times post FMT out competed non-commensal microbes (e.g. such as unclassified Clostridiales) for niche space. The selective advantage of these commensal microbes to occupy niches in the gastrointestinal tract helps to explain the success of FMT to reconstitute the gut microbe community of patients with recurrent C. difficile infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-015-0622-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-47111032016-01-14 Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile Kumar, Ranjit Maynard, Craig L. Eipers, Peter Goldsmith, Kelly T. Ptacek, Travis Grubbs, J. Aaron Dixon, Paula Howard, Donna Crossman, David K. Crowley, Michael R. Benjamin, William H. Lefkowitz, Elliot J. Weaver, Casey T. Rodriguez, J. Martin Morrow, Casey D. BMC Microbiol Research Article BACKGROUND: Fecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient’s gut commensal microbiota, we have analyzed the colonization potential of the donor, recipient and recipient post transplant fecal samples using transplantation in gnotobiotic mice. RESULTS: A total of nine samples from three human donors, recipient’s pre and post FMT were transplanted into gnotobiotic mice. Microbiome analysis of three donor fecal samples revealed the presence of a high relative abundance of commensal microbes from the family Bacteriodaceae and Lachnospiraceae that were almost absent in the three recipient pre FMT fecal samples (<0.01 %). The microbe composition in gnotobiotic mice transplanted with the donor fecal samples was similar to the human samples. The recipient samples contained Enterobacteriaceae, Lactobacillaceae, Enterococcaceae in relative abundance of 43, 11, 8 %, respectively. However, gnotobiotic mice transplanted with the recipient fecal samples had an average relative abundance of unclassified Clostridiales of 55 %, approximately 7000 times the abundance in the recipient fecal samples prior to transplant. Microbiome analysis of fecal samples from the three patients early (2–4 weeks) after FMT revealed a microbe composition with the relative abundance of both Bacteriodaceae and Lachnospiraceae that was approximately 7 % of that of the donor. In contrast, gnotobioitc mice transplanted with the fecal samples obtained from the three at early times post FMT revealed increases in the relative abundance of Bacteriodaceae and Lachnospiraceae microbe compositions to levels similar to the donor fecal samples. Furthermore, the unclassified Clostridiales in the recipient samples post FMT was reduced to an average of 10 %. CONCLUSION: We have used transplantation into gnotobiotic mice to evaluate the colonization potential of microbiota in FMT patients early after transplant. The commensal microbes present at early times post FMT out competed non-commensal microbes (e.g. such as unclassified Clostridiales) for niche space. The selective advantage of these commensal microbes to occupy niches in the gastrointestinal tract helps to explain the success of FMT to reconstitute the gut microbe community of patients with recurrent C. difficile infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-015-0622-2) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-13 /pmc/articles/PMC4711103/ /pubmed/26758906 http://dx.doi.org/10.1186/s12866-015-0622-2 Text en © Kumar et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kumar, Ranjit
Maynard, Craig L.
Eipers, Peter
Goldsmith, Kelly T.
Ptacek, Travis
Grubbs, J. Aaron
Dixon, Paula
Howard, Donna
Crossman, David K.
Crowley, Michael R.
Benjamin, William H.
Lefkowitz, Elliot J.
Weaver, Casey T.
Rodriguez, J. Martin
Morrow, Casey D.
Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile
title Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile
title_full Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile
title_fullStr Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile
title_full_unstemmed Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile
title_short Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile
title_sort colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent c. difficile
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711103/
https://www.ncbi.nlm.nih.gov/pubmed/26758906
http://dx.doi.org/10.1186/s12866-015-0622-2
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