Gut microbiota strain richness is species specific and affects engraftment

Alice Chen-Liaw¹, Varun Aggarwala^{1

2

3}, Ilaria Mogno^{1

2}, Craig Haifer^{4

5}, Zhihua Li^{1

2}, Joseph Eggers², Drew Helmus⁶, Amy Hart⁷, Jan Wehkamp⁷, Esi S N Lamousé-Smith⁷, Robert L Kerby⁸, Federico E Rey⁸, Jean Frédéric Colombel⁶, Michael A Kamm⁹, Bernat Olle¹⁰, Jason M Norman¹⁰, Rajita Menon¹⁰, Andrea R Watson¹⁰, Emily Crossette¹⁰, Elisabeth M Terveer^{11

12}, Josbert J Keller^{11

13

14}, Thomas J Borody¹⁵, Ari Grinspan⁶, Sudarshan Paramsothy^{4

16}, Nadeem O Kaakoush¹⁷, Marla C Dubinsky⁶, Jeremiah J Faith^{18

19}

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 Reliance Foundation Institution of Education and Research, Jio Institute, Navi Mumbai, India.
⁴ Concord Clinical School, University of Sydney, Sydney, New South Wales, Australia.
⁵ School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁶ Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁷ Janssen R&D, Spring House, PA, USA.
⁸ Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
⁹ Department of Gastroenterology and Medicine, St. Vincent's Hospital, Melbourne, Victoria, Australia.
¹⁰ Vedanta Biosciences, Cambridge, MA, USA.
¹¹ Netherlands Donor Feces Bank, Leiden University Medical Center, Leiden, The Netherlands.
¹² Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
¹³ Department of Gastroenterology, Haaglanden Medical Center, The Hague, The Netherlands.
¹⁴ Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁵ Centre for Digestive Diseases, Sydney, New South Wales, Australia.
¹⁶ Department of Gastroenterology and Hepatology, Macquarie University Hospital, Sydney, New South Wales, Australia.
¹⁷ School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
¹⁸ Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. jeremiah.faith@mssm.edu.
¹⁹ Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. jeremiah.faith@mssm.edu.

PMID: 39604726
PMCID: PMC12547691 (available on 2025-11-27)
DOI: 10.1038/s41586-024-08242-x

Gut microbiota strain richness is species specific and affects engraftment

Alice Chen-Liaw et al. Nature. 2025 Jan.

. 2025 Jan;637(8045):422-429.

doi: 10.1038/s41586-024-08242-x. Epub 2024 Nov 27.

Authors

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 Reliance Foundation Institution of Education and Research, Jio Institute, Navi Mumbai, India.
⁴ Concord Clinical School, University of Sydney, Sydney, New South Wales, Australia.
⁵ School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁶ Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁷ Janssen R&D, Spring House, PA, USA.
⁸ Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
⁹ Department of Gastroenterology and Medicine, St. Vincent's Hospital, Melbourne, Victoria, Australia.
¹⁰ Vedanta Biosciences, Cambridge, MA, USA.
¹¹ Netherlands Donor Feces Bank, Leiden University Medical Center, Leiden, The Netherlands.
¹² Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
¹³ Department of Gastroenterology, Haaglanden Medical Center, The Hague, The Netherlands.
¹⁴ Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁵ Centre for Digestive Diseases, Sydney, New South Wales, Australia.
¹⁶ Department of Gastroenterology and Hepatology, Macquarie University Hospital, Sydney, New South Wales, Australia.
¹⁷ School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
¹⁸ Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. jeremiah.faith@mssm.edu.
¹⁹ Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. jeremiah.faith@mssm.edu.

PMID: 39604726
PMCID: PMC12547691 (available on 2025-11-27)
DOI: 10.1038/s41586-024-08242-x

Erratum in

Author Correction: Gut microbiota strain richness is species specific and affects engraftment.
Chen-Liaw A, Aggarwala V, Mogno I, Haifer C, Li Z, Eggers J, Helmus D, Hart A, Wehkamp J, Lamousé-Smith ESN, Kerby RL, Rey FE, Colombel JF, Kamm MA, Olle B, Norman JM, Menon R, Watson AR, Crossette E, Terveer EM, Keller JJ, Borody TJ, Grinspan A, Paramsothy S, Kaakoush NO, Dubinsky MC, Faith JJ. Chen-Liaw A, et al. Nature. 2025 Feb;638(8050):E4. doi: 10.1038/s41586-024-08566-8. Nature. 2025. PMID: 39875608 No abstract available.

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: J.J.F. is a scientific advisory board member and consultant to Vedanta Biosciences, Inc. A.H., J.W., E.S.N.L.-S. are employees of Janssen Research & Development. B.O., J.M.N., R.M., A.R.W. and E.C. are employees of Vedanta Biosciences. J.K. and E.T. received research grants from Vedanta Biosciences. The remaining authors declare no competing interests.

References

1. Yang C et al. Immunoglobulin A antibody composition is sculpted to bind the self gut microbiome. Sci. Immunol. 7, eabg3208 (2022). - PMC - PubMed
1. Parida S et al. A procarcinogenic colon microbe promotes breast tumorigenesis and metastatic progression and concomitantly activates notch and β-catenin axes. Cancer Discov. 11, 1138–1157 (2021). - PubMed
1. Arthur JC et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338, 120–123 (2012). - PMC - PubMed
1. Britton GJ et al. Defined microbiota transplant restores Th17/RORγt⁺ regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas. Proc Natl Acad. Sci. USA 117, 21536–21545 (2020). - PMC - PubMed
1. Yang C et al. Fecal IgA levels are determined by strain-level differences in bacteroides ovatus and are modifiable by gut microbiota manipulation. Cell Host Microbe 27, 467–475.e6 (2020). - PMC - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Gut microbiota strain richness is species specific and affects engraftment

Affiliations

Gut microbiota strain richness is species specific and affects engraftment

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials