Identification of clinical and ecological determinants of strain engraftment after fecal microbiota transplantation using metagenomics
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Abstract
ABSTRACT Fecal microbiota transplantation (FMT) is both a promising therapeutic approach to treat microbiota-associated pathologies and an experimental tool to establish a causal role of microbiome dysbiosis in human pathologies. Although clearly efficacious in resolving recurrent Clostridioides difficile infection (rCDI), the therapeutic value of FMT in other pathologies is not yet established, and our mechanistic and ecological understanding of how FMT alters the microbiome in patients is incomplete. Here, we assembled the most comprehensive FMT trial microbiota dataset to date, including new and previously generated fecal metagenomes from FMT trials in rCDI, inflammatory bowel disease (IBD), metabolic syndrome (MetS), drug-resistant pathogen colonization (MDR), and resistance to immune checkpoint inhibitor anti-tumor therapy (ICI). We characterized post-FMT microbiota assembly in the recipients by establishing the origin of the detected strains, and we identified the clinical and ecological factors that determine the engraftment of donor strains. Our findings showed little coexistence of donor and recipient strains and linked the magnitude of donor strain engraftment to dysbiosis of the recipient microbiome. Dysbiosis and strain engraftment were low in pathologies other than rCDI but could be enhanced through pretreatment with antibiotics and lavage. Using generalized linear mixed-effects models, we demonstrate that both ecological (low recipient and high donor ɑ-diversity and relative species abundance) and clinical (antibiotic pretreatment, bowel lavage, multiple rounds of FMT) variables are associated with increased donor microbiota engraftment, and that donor strain engraftment events are predictable for individual patients and strains. Overall donor strain engraftment was not linked to FMT outcome in IBD patients but was higher in ICI patients that responded to immunotherapy after FMT. Our findings provide an ecological framework for post-FMT microbiota assembly that can predict donor strain engraftment and determine its importance for clinical outcomes, informing more targeted and personalized approaches to increase the therapeutic benefits of FMTs.
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In the TURN trial, the post-FMT microbiome of recipients who experienced clinical success was more similar to the microbiome of their corresponding donors than to their microbiome before FMT, with a shift in beta diversity.
“In the TURN trial, the post-FMT microbiome of recipients who experienced clinical success was more similar to the microbiome of their corresponding donors than to their microbiome before FMT, with a shift in their beta diversity. 60”
From Key determinants of success in fecal microbiota transplantation: From microbiome to clinic (2023) · cites this paper as [60]
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- Authors
- Podlesny, D., Durdevic, M., Paramsothy, S., Kaakoush, N. O., Högenauer, C., Gorkiewicz, G., Walter, J., & Fricke, W. F.
- Affiliations
- University of Hohenheim (DE)
- The University of Sydney (AU)
- UNSW Sydney (AU)
- Medical University of Graz (AT)
- University College Cork (IE)
- Corresponding author
- Podlesny, Daniel
- Fricke, W. Florian
- ORCID
- Venue
- Cell Reports Medicine
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 3
- Issue
- 8
- Pages
- 100711
- ISSN
- 2666-3791 (ISSN-L)
- PMC
- PMC9418803
- OpenAlex
- W4289835872
- Cited by
- 111
- References
- 103
- Citations by year
- 2026: 19 · 2025: 41 · 2024: 37 · 2023: 10 · 2022: 4
- FWCI
- 7.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports Medicine (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (316130265)
- Austrian Science Fund (DK-MOLIN W1241)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- fecal microbiota transplantation, microbiome assembly, dysbiosis, antibiotic pretreatment, alpha diversity, strain coexistence, oral microbiota, Gram-positive bacteria, oxygen tolerance
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Clostridium Infections, Humans, Metagenomics, Dysbiosis
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