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Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients

Eli L. Moss, Shannon B. Falconer, Ekaterina Tkachenko, Mingjie Wang, Hannah Systrom, Jasmin Mahabamunuge, David A. Relman, Elizabeth L. Hohmann, Ami S. Bhatt
doi: https://doi.org/10.1101/109645
Eli L. Moss
2Departments of Genetics, and Medicine, Stanford University, Stanford, California, USA.
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Shannon B. Falconer
3Departments of Microbiology and Immunology, and Medicine, Stanford University, Stanford, California, USA.
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Ekaterina Tkachenko
2Departments of Genetics, and Medicine, Stanford University, Stanford, California, USA.
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Mingjie Wang
2Departments of Genetics, and Medicine, Stanford University, Stanford, California, USA.
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Hannah Systrom
4Division of Infectious Diseases, Massachusetts General Hospital; Harvard Medical School, Boston, Massachusetts, USA.
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Jasmin Mahabamunuge
4Division of Infectious Diseases, Massachusetts General Hospital; Harvard Medical School, Boston, Massachusetts, USA.
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David A. Relman
3Departments of Microbiology and Immunology, and Medicine, Stanford University, Stanford, California, USA.
5Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
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Elizabeth L. Hohmann
4Division of Infectious Diseases, Massachusetts General Hospital; Harvard Medical School, Boston, Massachusetts, USA.
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  • For correspondence: ehohmann@partners.org asbhatt@stanford.edu
Ami S. Bhatt
2Departments of Genetics, and Medicine, Stanford University, Stanford, California, USA.
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  • For correspondence: ehohmann@partners.org asbhatt@stanford.edu
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Abstract

Immunocompromised individuals are at high risk of developing Clostridium difficile-associated disease (CDAD). Fecal microbiota transplantation (FMT) is a highly effective therapy for refractory or recurrent CDAD and, despite safety concerns, has recently been offered to immunocompromised patients. We investigated the genomics of bacterial composition following FMT in immunocompromised patients over a 1-year period. Metagenomic, strain and gene-level bacterial dynamics were characterized in two CDAD-affected hematopoietic stem cell (HCT) recipients following FMT. We found alterations in gene content, including loss of virulence and antibiotic resistance genes. These alterations were accompanied by long-term bacterial divergence at the species and strain levels. Our findings suggest limited durability of the specific bacterial consortium introduced with FMT and indicate that alterations of the functional potential of the microbiome are more complex than can be inferred by taxonomic information alone. Our observation that FMT alone cannot induce long-term donor-like alterations of the microbiota of HCT recipients suggests that FMT cannot indefinitely supersede environmental and/or host factors in shaping bacterial composition.

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Posted February 18, 2017.
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Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients
Eli L. Moss, Shannon B. Falconer, Ekaterina Tkachenko, Mingjie Wang, Hannah Systrom, Jasmin Mahabamunuge, David A. Relman, Elizabeth L. Hohmann, Ami S. Bhatt
bioRxiv 109645; doi: https://doi.org/10.1101/109645
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Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients
Eli L. Moss, Shannon B. Falconer, Ekaterina Tkachenko, Mingjie Wang, Hannah Systrom, Jasmin Mahabamunuge, David A. Relman, Elizabeth L. Hohmann, Ami S. Bhatt
bioRxiv 109645; doi: https://doi.org/10.1101/109645

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