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Title: Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics

Abstract

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection and shows promise for treating other medical conditions associated with intestinal dysbioses. However, we lack a sufficient understanding of which microbial populations successfully colonize the recipient gut, and the widely used approaches to study the microbial ecology of FMT experiments fail to provide enough resolution to identify populations that are likely responsible for FMT-derived benefits. Here, we used shotgun metagenomics together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from fecal samples of a single FMT donor. We then used metagenomic mapping to track the occurrence and distribution patterns of donor MAGs in two FMT recipients. Our analyses revealed that 22% of the 92 highly complete bacterial MAGs that we identified from the donor successfully colonized and remained abundant in two recipients for at least 8 weeks. Most MAGs with a high colonization rate belonged to the order Bacteroidales. The vast majority of those that lacked evidence of colonization belonged to the order Clostridiales, and colonization success was negatively correlated with the number of genes related to sporulation. Our analysis of 151 publicly available gut metagenomes showed that the donor MAGs that colonized both recipientsmore » were prevalent, and the ones that colonized neither were rare across the participants of the Human Microbiome Project. Although our dataset showed a link between taxonomy and the colonization ability of a given MAG, we also identified MAGs that belong to the same taxon with different colonization properties, highlighting the importance of an appropriate level of resolution to explore the functional basis of colonization and to identify targets for cultivation, hypothesis generation, and testing in model systems. Lastly, the analytical strategy adopted in our study can provide genomic insights into bacterial populations that may be critical to the efficacy of FMT due to their success in gut colonization and metabolic properties, and guide cultivation efforts to investigate mechanistic underpinnings of this procedure beyond associations.« less

Authors:
 [1];  [2];  [1];  [1];  [1];  [1];  [3];  [1];  [1];  [4]
  1. Univ. of Chicago Medicine, Chicago, IL (United States)
  2. Univ. of Chicago Medicine, Chicago, IL (United States); Boston Children's Hospital, Boston, MA (United States)
  3. Marine Biological Lab., Woods Hole, MA (United States)
  4. Univ. of Chicago Medicine, Chicago, IL (United States); Marine Biological Lab., Woods Hole, MA (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
Gastro-Intestinal Research Foundation (GIRF); University of Chicago; USDOE
OSTI Identifier:
1415981
Grant/Contract Number:
AC02-06CH11357
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Microbiome
Additional Journal Information:
Journal Volume: 5; Journal Issue: 1; Journal ID: ISSN 2049-2618
Publisher:
BioMed Central
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; colonization; fecal microbiota transplantation; metagenome-assembled genomes; metagenomics

Citation Formats

Lee, Sonny T. M., Kahn, Stacy A., Delmont, Tom O., Shaiber, Alon, Esen, Ozcan C., Hubert, Nathaniel A., Morrison, Hilary G., Antonopoulos, Dionysios A., Rubin, David T., and Eren, A. Murat. Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics. United States: N. p., 2017. Web. doi:10.1186/s40168-017-0270-x.
Lee, Sonny T. M., Kahn, Stacy A., Delmont, Tom O., Shaiber, Alon, Esen, Ozcan C., Hubert, Nathaniel A., Morrison, Hilary G., Antonopoulos, Dionysios A., Rubin, David T., & Eren, A. Murat. Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics. United States. doi:10.1186/s40168-017-0270-x.
Lee, Sonny T. M., Kahn, Stacy A., Delmont, Tom O., Shaiber, Alon, Esen, Ozcan C., Hubert, Nathaniel A., Morrison, Hilary G., Antonopoulos, Dionysios A., Rubin, David T., and Eren, A. Murat. 2017. "Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics". United States. doi:10.1186/s40168-017-0270-x. https://www.osti.gov/servlets/purl/1415981.
@article{osti_1415981,
title = {Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics},
author = {Lee, Sonny T. M. and Kahn, Stacy A. and Delmont, Tom O. and Shaiber, Alon and Esen, Ozcan C. and Hubert, Nathaniel A. and Morrison, Hilary G. and Antonopoulos, Dionysios A. and Rubin, David T. and Eren, A. Murat},
abstractNote = {Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection and shows promise for treating other medical conditions associated with intestinal dysbioses. However, we lack a sufficient understanding of which microbial populations successfully colonize the recipient gut, and the widely used approaches to study the microbial ecology of FMT experiments fail to provide enough resolution to identify populations that are likely responsible for FMT-derived benefits. Here, we used shotgun metagenomics together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from fecal samples of a single FMT donor. We then used metagenomic mapping to track the occurrence and distribution patterns of donor MAGs in two FMT recipients. Our analyses revealed that 22% of the 92 highly complete bacterial MAGs that we identified from the donor successfully colonized and remained abundant in two recipients for at least 8 weeks. Most MAGs with a high colonization rate belonged to the order Bacteroidales. The vast majority of those that lacked evidence of colonization belonged to the order Clostridiales, and colonization success was negatively correlated with the number of genes related to sporulation. Our analysis of 151 publicly available gut metagenomes showed that the donor MAGs that colonized both recipients were prevalent, and the ones that colonized neither were rare across the participants of the Human Microbiome Project. Although our dataset showed a link between taxonomy and the colonization ability of a given MAG, we also identified MAGs that belong to the same taxon with different colonization properties, highlighting the importance of an appropriate level of resolution to explore the functional basis of colonization and to identify targets for cultivation, hypothesis generation, and testing in model systems. Lastly, the analytical strategy adopted in our study can provide genomic insights into bacterial populations that may be critical to the efficacy of FMT due to their success in gut colonization and metabolic properties, and guide cultivation efforts to investigate mechanistic underpinnings of this procedure beyond associations.},
doi = {10.1186/s40168-017-0270-x},
journal = {Microbiome},
number = 1,
volume = 5,
place = {United States},
year = 2017,
month = 5
}

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