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Gut microbiota strain richness is species specific and affects engraftment

Author

Listed:
  • Alice Chen-Liaw

    (Icahn School of Medicine at Mount Sinai)

  • Varun Aggarwala

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Jio Institute)

  • Ilaria Mogno

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Craig Haifer

    (University of Sydney
    University of New South Wales)

  • Zhihua Li

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Joseph Eggers

    (Icahn School of Medicine at Mount Sinai)

  • Drew Helmus

    (Icahn School of Medicine at Mount Sinai)

  • Amy Hart

    (Janssen R&D)

  • Jan Wehkamp

    (Janssen R&D)

  • Esi S. N. Lamousé-Smith

    (Janssen R&D)

  • Robert L. Kerby

    (University of Wisconsin—Madison)

  • Federico E. Rey

    (University of Wisconsin—Madison)

  • Jean Frédéric Colombel

    (Icahn School of Medicine at Mount Sinai)

  • Michael A. Kamm

    (St. Vincent’s Hospital)

  • Bernat Olle

    (Vedanta Biosciences)

  • Jason M. Norman

    (Vedanta Biosciences)

  • Rajita Menon

    (Vedanta Biosciences)

  • Andrea R. Watson

    (Vedanta Biosciences)

  • Emily Crossette

    (Vedanta Biosciences)

  • Elisabeth M. Terveer

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Josbert J. Keller

    (Leiden University Medical Center
    Haaglanden Medical Center
    Leiden University Medical Center)

  • Thomas J. Borody

    (Centre for Digestive Diseases)

  • Ari Grinspan

    (Icahn School of Medicine at Mount Sinai)

  • Sudarshan Paramsothy

    (University of Sydney
    Macquarie University Hospital)

  • Nadeem O. Kaakoush

    (University of New South Wales)

  • Marla C. Dubinsky

    (Icahn School of Medicine at Mount Sinai)

  • Jeremiah J. Faith

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

Abstract

Despite the fundamental role of bacterial strain variation in gut microbiota function1–6, the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments. Active therapeutic administration of supraphysiologic numbers of strains per species increases recipient SR, which then converges back to the population average after dosing is ceased. Stratifying engraftment outcomes by high or low SR shows that SR predicts microbial addition or replacement in faecal transplants. Together, these results indicate that properties of the gut ecosystem govern the number of strains of each species colonizing the gut and thereby influence strain addition and replacement in faecal microbiota transplantation and defined live biotherapeutic products.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:nature:v:637:y:2025:i:8045:d:10.1038_s41586-024-08242-x
    DOI: 10.1038/s41586-024-08242-x
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