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

Autor: Lee STM; Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, IL, USA., Kahn SA; Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.; Present address: Boston Children's Hospital, Inflammatory Bowel Disease Center, Boston, MA, USA., Delmont TO; Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, IL, USA., Shaiber A; Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, IL, USA., Esen ÖC; Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, IL, USA., Hubert NA; Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, IL, USA., Morrison HG; Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, 02543, MA, USA., Antonopoulos DA; Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, IL, USA., Rubin DT; Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, IL, USA., Eren AM; Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, IL, USA. meren@uchicago.edu.; Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, 02543, MA, USA. meren@uchicago.edu.
Jazyk: angličtina
Zdroj: Microbiome [Microbiome] 2017 May 04; Vol. 5 (1), pp. 50. Date of Electronic Publication: 2017 May 04.
DOI: 10.1186/s40168-017-0270-x
Abstrakt: Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Databáze: MEDLINE
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