Identification of clinical and ecological determinants of strain engraftment after fecal microbiota transplantation using metagenomics
Daniel Podlesny, Marija Durdevic, Sudarshan Paramsothy, Nadeem O Kaakoush, Christoph Högenauer, Gregor Gorkiewicz, Jens Walter, W Florian Fricke, Daniel Podlesny, Marija Durdevic, Sudarshan Paramsothy, Nadeem O Kaakoush, Christoph Högenauer, Gregor Gorkiewicz, Jens Walter, W Florian Fricke
Abstract
Fecal microbiota transplantation (FMT) is a promising therapeutic approach for microbiota-associated pathologies, but our understanding of the post-FMT microbiome assembly process and its ecological and clinical determinants is incomplete. Here we perform a comprehensive fecal metagenome analysis of 14 FMT trials, involving five pathologies and >250 individuals, and determine the origins of strains in patients after FMT. Independently of the underlying clinical condition, conspecific coexistence of donor and recipient strains after FMT is uncommon and donor strain engraftment is strongly positively correlated with pre-FMT recipient microbiota dysbiosis. Donor strain engraftment was enhanced through antibiotic pretreatment and bowel lavage and dependent on donor and recipient ɑ-diversity; strains from relatively abundant species were more likely and from predicted oral, oxygen-tolerant, and gram-positive species less likely to engraft. We introduce a general mechanistic framework for post-FMT microbiome assembly in alignment with ecological theory, which can guide development of optimized, more targeted, and personalized FMT therapies.
Keywords: donor strain engraftment; dysbiosis; ecological theory; fecal microbiota transplantation; metagenomics; microbiota depletion; personalized FMT; post-FMT microbiome assembly; shared strain analysis.
Conflict of interest statement
Declaration of interests The authors declare no competing interests.
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
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References
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