Gut microbiota strain richness is species specific and affects engraftment

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 Frédéric Colombel, Michael A. Kamm, Bernat Olle, Jason M. Norman, Rajita Menon, Andrea R. Watson, Emily Crossette, Elisabeth M. Terveer, Josbert J. Keller, Thomas J. Borody, Ari Grinspan, Sudarshan Paramsothy, Nadeem O. Kaakoush, Marla C. Dubinsky and Jeremiah J. Faith ()
Additional contact information
Alice Chen-Liaw: Icahn School of Medicine at Mount Sinai
Varun Aggarwala: Icahn School of Medicine at Mount Sinai
Ilaria Mogno: Icahn School of Medicine at Mount Sinai
Craig Haifer: University of Sydney
Zhihua Li: 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
Josbert J. Keller: 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
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

Nature, 2025, vol. 637, issue 8045, 422-429

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41586-024-08242-x

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