Abstract
Original language | English |
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Pages (from-to) | 1902-1912 |
Number of pages | 11 |
Journal | Nature medicine |
Volume | 28 |
Issue number | 9 |
DOIs | |
Publication status | Published - 1 Sept 2022 |
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In: Nature medicine, Vol. 28, No. 9, 01.09.2022, p. 1902-1912.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Drivers and determinants of strain dynamics following fecal microbiota transplantation
AU - Schmidt, Thomas S. B.
AU - Li, Simone S.
AU - Maistrenko, Oleksandr M.
AU - Akanni, Wasiu
AU - Coelho, Luis Pedro
AU - Dolai, Sibasish
AU - Fullam, Anthony
AU - Glazek, Anna M.
AU - Hercog, Rajna
AU - Herrema, Hilde
AU - Jung, Ferris
AU - Kandels, Stefanie
AU - Orakov, Askarbek
AU - Thielemann, Roman
AU - von Stetten, Moritz
AU - van Rossum, Thea
AU - Benes, Vladimir
AU - Borody, Thomas J.
AU - de Vos, Willem M.
AU - Ponsioen, Cyriel Y.
AU - Nieuwdorp, Max
AU - Bork, Peer
N1 - Funding Information: T.J.B. has a pecuniary interest in the Centre for Digestive Diseases in Australia and holds patents in the use of FMT for gastrointestinal diseases. C.Y.P. received funding grants from Gilead and Perspectum, speaker’s fees from Tillotts and consultancy fees from Shire and Pliant. M.N. and W.M.d.V. are founders and members of the Scientific Advisory Board of Caelus Health (the Netherlands). M.N. is a Scientific Advisory Board member of Kaleido Biosciences (USA). W.M.d.V. is founder and Scientific Advisory Board member of A-mansia Biotech (Belgium). These conflicts bear no relevance to the content of this manuscript. Funding Information: We thank A. Moss (Harvard University, USA), C. Morrow (University of Alabama at Birmingham, USA), S. Leo (University of Geneva, Switzerland), R. Goll (University of Tromsø, Norway) and D. Podlesny (University of Hohenheim, Germany) for providing additional information on the cohorts used in this study. We further thank R. J. Alves, A. Schwartz, M. Kuhn, P. Ferretti, S. K. Forslund and members of the Bork laboratory at EMBL for support and constructive discussions. This work was supported by the European Research Council under the European Union’s Horizon2020 research and innovation program (nos. ERC-AdG-669830 to T.S.B.S., S.S.L., O.M.M., R.H., F.J. and P.B.; and ERC-AdG-686070 to L.P.C. and T.V.R.), by the German Federal Ministry of Education and Research (LAMarCK, no. 031L0181A to A.O.) and by the European Molecular Biology Laboratory (to W.A., A.F., A.M.G., S.K., R.T., M.v.S., V.B. and P.B.). S.S.L. acknowledges support from the European Molecular Biology Organisation (no. ALTF 137-2018) and the National Health and Medical Research Council of Australia (no. APP1166180). H.H. is supported by a Senior Fellowship of the Dutch Diabetes Research Foundation (no. 2019.82.004). W.M.d.V. is supported by the Spinoza 2008 award and a SIAM Gravitation grant from the Netherlands Organization for Scientific Research (no. 024.002.002). M.N. is supported by a ZONMW VICI grant 2020 (no. 09150182010020). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Funding Information: We thank A. Moss (Harvard University, USA), C. Morrow (University of Alabama at Birmingham, USA), S. Leo (University of Geneva, Switzerland), R. Goll (University of Tromsø, Norway) and D. Podlesny (University of Hohenheim, Germany) for providing additional information on the cohorts used in this study. We further thank R. J. Alves, A. Schwartz, M. Kuhn, P. Ferretti, S. K. Forslund and members of the Bork laboratory at EMBL for support and constructive discussions. This work was supported by the European Research Council under the European Union’s Horizon2020 research and innovation program (nos. ERC-AdG-669830 to T.S.B.S., S.S.L., O.M.M., R.H., F.J. and P.B.; and ERC-AdG-686070 to L.P.C. and T.V.R.), by the German Federal Ministry of Education and Research (LAMarCK, no. 031L0181A to A.O.) and by the European Molecular Biology Laboratory (to W.A., A.F., A.M.G., S.K., R.T., M.v.S., V.B. and P.B.). S.S.L. acknowledges support from the European Molecular Biology Organisation (no. ALTF 137-2018) and the National Health and Medical Research Council of Australia (no. APP1166180). H.H. is supported by a Senior Fellowship of the Dutch Diabetes Research Foundation (no. 2019.82.004). W.M.d.V. is supported by the Spinoza 2008 award and a SIAM Gravitation grant from the Netherlands Organization for Scientific Research (no. 024.002.002). M.N. is supported by a ZONMW VICI grant 2020 (no. 09150182010020). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Publisher Copyright: © 2022, The Author(s).
PY - 2022/9/1
Y1 - 2022/9/1
N2 - Fecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor–recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.
AB - Fecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor–recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.
UR - http://www.scopus.com/inward/record.url?scp=85138172313&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41591-022-01913-0
DO - https://doi.org/10.1038/s41591-022-01913-0
M3 - Article
C2 - 36109636
SN - 1078-8956
VL - 28
SP - 1902
EP - 1912
JO - Nature medicine
JF - Nature medicine
IS - 9
ER -