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

doi:10.1016/j.xcrm.2022.100711

Identification of clinical and ecological determinants of strain engraftment after fecal microbiota transplantation using metagenomics

Cell Rep Med. 2022 Aug 16;3(8):100711. doi: 10.1016/j.xcrm.2022.100711. Epub 2022 Aug 4.

Authors

Daniel Podlesny¹, Marija Durdevic², Sudarshan Paramsothy³, Nadeem O Kaakoush⁴, Christoph Högenauer⁵, Gregor Gorkiewicz⁶, Jens Walter⁷, W Florian Fricke⁸

Affiliations

¹ Department of Microbiome Research and Applied Bioinformatics, University of Hohenheim, Stuttgart, Germany. Electronic address: daniel.podlesny@uni-hohenheim.de.
² Institute of Pathology, Medical University of Graz, Graz, Austria; Theodor Escherich Laboratory for Medical Microbiome Research, Medical University of Graz, Graz, Austria.
³ Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, NSW, Australia; Concord Clinical School, University of Sydney, Sydney, NSW, Australia.
⁴ School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia.
⁵ Institute of Pathology, Medical University of Graz, Graz, Austria; Theodor Escherich Laboratory for Medical Microbiome Research, Medical University of Graz, Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁶ Institute of Pathology, Medical University of Graz, Graz, Austria; Theodor Escherich Laboratory for Medical Microbiome Research, Medical University of Graz, Graz, Austria; BioTechMed, Interuniversity Cooperation, Graz, Austria.
⁷ APC Microbiome Ireland, School of Microbiology and Department of Medicine, University College Cork, Cork, Ireland.
⁸ Department of Microbiome Research and Applied Bioinformatics, University of Hohenheim, Stuttgart, Germany; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: w.florian.fricke@uni-hohenheim.de.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Clostridium Infections* / therapy
Dysbiosis / therapy
Fecal Microbiota Transplantation
Gastrointestinal Microbiome* / genetics
Humans
Metagenomics