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Detecting microbial engraftment after FMT using placebo sequencing and culture enriched metagenomics to sort signals from noise

Author

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  • Shahrokh Shekarriz

    (McMaster University
    Farncombe Family Digestive Health Research, Institute McMaster University)

  • Jake C. Szamosi

    (McMaster University
    Farncombe Family Digestive Health Research, Institute McMaster University)

  • Fiona J. Whelan

    (University of Manchester)

  • Jennifer T. Lau

    (Farncombe Family Digestive Health Research, Institute McMaster University)

  • Josie Libertucci

    (Farncombe Family Digestive Health Research, Institute McMaster University)

  • Laura Rossi

    (McMaster University
    Farncombe Family Digestive Health Research, Institute McMaster University)

  • Michelle E. Fontes

    (McMaster University
    Farncombe Family Digestive Health Research, Institute McMaster University)

  • Melanie Wolfe

    (McMaster University
    Farncombe Family Digestive Health Research, Institute McMaster University)

  • Christine H. Lee

    (The University of British Columbia)

  • Paul Moayyedi

    (McMaster University
    Farncombe Family Digestive Health Research, Institute McMaster University)

  • Michael G. Surette

    (McMaster University
    Farncombe Family Digestive Health Research, Institute McMaster University
    McMaster University)

Abstract

Fecal microbiota transplantation (FMT) has shown efficacy for the treatment of ulcerative colitis but with variable response between patients and trials. The mechanisms underlying FMT’s therapeutic effects remains poorly understood but is generally assumed to involve engraftment of donor microbiota into the recipient’s microbiome. Reports of microbial engraftment following FMT have been inconsistent between studies. Here, we investigate microbial engraftment in a previous randomized controlled trial (NCT01545908), in which FMT was sourced from a single donor, using amplicon-based profiling, shotgun metagenomics, and culture-enriched metagenomics. Placebo samples were included to estimate engraftment noise, and a significant level of false-positive engraftment was observed which confounds the prediction of true engraftment. We show that analyzing engraftment across multiple patients from a single donor enhances the accuracy of detection. We identified a unique set of genes engrafted in responders to FMT which supports strain displacement as the primary mechanism of engraftment in our cohort.

Suggested Citation

  • Shahrokh Shekarriz & Jake C. Szamosi & Fiona J. Whelan & Jennifer T. Lau & Josie Libertucci & Laura Rossi & Michelle E. Fontes & Melanie Wolfe & Christine H. Lee & Paul Moayyedi & Michael G. Surette, 2025. "Detecting microbial engraftment after FMT using placebo sequencing and culture enriched metagenomics to sort signals from noise," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58673-x
    DOI: 10.1038/s41467-025-58673-x
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    References listed on IDEAS

    as
    1. Mireia Valles-Colomer & Aitor Blanco-Míguez & Paolo Manghi & Francesco Asnicar & Leonard Dubois & Davide Golzato & Federica Armanini & Fabio Cumbo & Kun D. Huang & Serena Manara & Giulia Masetti & Fed, 2023. "The person-to-person transmission landscape of the gut and oral microbiomes," Nature, Nature, vol. 614(7946), pages 125-135, February.
    2. Alice Chen-Liaw & Varun Aggarwala & Ilaria Mogno & Craig Haifer & Zhihua Li & Joseph Eggers & Drew Helmus & Amy Hart & Jan Wehkamp & Esi S. N. Lamousé-Smith & Robert L. Kerby & Federico E. Rey & Jean , 2025. "Author Correction: Gut microbiota strain richness is species specific and affects engraftment," Nature, Nature, vol. 638(8050), pages 4-4, February.
    3. repec:plo:pone00:0061217 is not listed on IDEAS
    4. Hilary P. Browne & Samuel C. Forster & Blessing O. Anonye & Nitin Kumar & B. Anne Neville & Mark D. Stares & David Goulding & Trevor D. Lawley, 2016. "Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation," Nature, Nature, vol. 533(7604), pages 543-546, May.
    5. Alice Chen-Liaw & Varun Aggarwala & Ilaria Mogno & Craig Haifer & Zhihua Li & Joseph Eggers & Drew Helmus & Amy Hart & Jan Wehkamp & Esi S. N. Lamousé-Smith & Robert L. Kerby & Federico E. Rey & Jean , 2025. "Gut microbiota strain richness is species specific and affects engraftment," Nature, Nature, vol. 637(8045), pages 422-429, January.
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