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 Crossett; Elisabeth M Terveer; Josbert J Keller; Thomas J Borody; Ari Grinspan; Sudarshan Paramsothy; Nadeem O Kaakoush; Marla C Dubinsky; Jeremiah J Faith

doi:10.1038/s41586-024-08242-x

Gut microbiota strain richness is species specific and affects engraftment

Nature. 2024 Nov 27. doi: 10.1038/s41586-024-08242-x. Online ahead of print.

Authors

Alice Chen-Liaw¹, Varun Aggarwala^{1

2}, Ilaria Mogno^{1

2}, Craig Haifer^{3

4}, Zhihua Li^{1

2}, Joseph Eggers², Drew Helmus⁵, Amy Hart⁶, Jan Wehkamp⁶, Esi S N Lamousé-Smith⁶, Robert L Kerby⁷, Federico E Rey⁷, Jean Frédéric Colombel⁵, Michael A Kamm⁸, Bernat Olle⁹, Jason M Norman⁹, Rajita Menon⁹, Andrea R Watson⁹, Emily Crossett⁹, Elisabeth M Terveer^{10

11}, Josbert J Keller^{10

12

13}, Thomas J Borody¹⁴, Ari Grinspan⁵, Sudarshan Paramsothy^{3

15}, Nadeem O Kaakoush¹⁶, Marla C Dubinsky⁵, Jeremiah J Faith^{17

18}

Affiliations

¹ Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³ Concord Clinical School, University of Sydney, Sydney, New South Wales, Australia.
⁴ School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Janssen R&D, Spring House, PA, USA.
⁷ Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
⁸ Department of Gastroenterology and Medicine, St. Vincent's Hospital, Melbourne, Victoria, Australia.
⁹ Vedanta Biosciences, Cambridge, MA, USA.
¹⁰ Netherlands Donor Feces Bank, Leiden University Medical Center, Leiden, The Netherlands.
¹¹ Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
¹² Department of Gastroenterology, Haaglanden Medical Center, The Hague, The Netherlands.
¹³ Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁴ Centre for Digestive Diseases, Sydney, New South Wales, Australia.
¹⁵ Department of Gastroenterology and Hepatology, Macquarie University Hospital, Sydney, New South Wales, Australia.
¹⁶ School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
¹⁷ Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected].
¹⁸ Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected].

PMID: 39604726
DOI: 10.1038/s41586-024-08242-x

Abstract

Despite the fundamental role of bacterial strain variation in gut microbiota function^1-6, 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.