Environment dominates over host genetics in shaping human gut microbiota

Daphna Rothschild; Omer Weissbrod; Elad Barkan; Alexander Kurilshikov; Tal Korem; David Zeevi; Paul I. Costea; Anastasia Godneva; Iris N. Kalka; Noam Bar; Smadar Shilo; Dar Lador; Arnau Vich Vila; Niv Zmora; Meirav Pevsner-Fischer; David Israeli; Noa Kosower; Gal Malka; Bat Chen Wolf; Tali Avnit-Sagi; Maya Lotan-Pompan; Adina Weinberger; Zamir Halpern; Shai Carmi; Jingyuan Fu; Cisca Wijmenga; Alexandra Zhernakova; Eran Elinav; Eran Segal

doi:10.1038/nature25973

Environment dominates over host genetics in shaping human gut microbiota

Daphna Rothschild, Omer Weissbrod, Elad Barkan, Alexander Kurilshikov, Tal Korem, David Zeevi, Paul I. Costea, Anastasia Godneva, Iris N. Kalka, Noam Bar, Smadar Shilo, Dar Lador, Arnau Vich Vila, Niv Zmora, Meirav Pevsner-Fischer, David Israeli, Noa Kosower, Gal Malka, Bat Chen Wolf, Tali Avnit-SagiMaya Lotan-Pompan, Adina Weinberger, Zamir Halpern, Shai Carmi, Jingyuan Fu, Cisca Wijmenga, Alexandra Zhernakova, Eran Elinav^*, Eran Segal

^*Corresponding author for this work

Department of Social Medicine

Research output: Contribution to journal › Article › peer-review

1517 Scopus citations

Abstract

Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

Original language	American English
Pages (from-to)	210-215
Number of pages	6
Journal	Nature
Volume	555
Issue number	7695
DOIs	https://doi.org/10.1038/nature25973
State	Published - 8 Mar 2018

Bibliographical note

Funding Information:
The project was provided by the Wellcome Trust under awards 076113 and 085475. E.S. is supported by the Crown Human Genome Center; the Else Kroener Fresenius Foundation; D. L. Schwarz; J. N. Halpern; L. Steinberg; and grants funded by the European Research Council and the Israel Science Foundation. E.E. is supported by Y. and R. Ungar, the Gurwin Family Fund for Scientific Research, the Leona M. and Harry B. Helmsley Charitable Trust, the Israel Science Foundation and the Helmholtz Foundation. E.E. holds the Sir Marc and Lady Tania Feldmann Professorial Chair in Immunology, is a senior fellow of the Canadian Institute for Advanced Research, and is an international scholar at the Bill and Melinda Gates Foundation and Howard Hughes Medical Institute. D.R. received a Levi Eshkol PhD Scholarship for Personalized Medicine by the Israeli Ministry of Science. LLD was made possible by grants from the Top Institute Food and Nutrition (GH001) to C.W. C.W. is funded by a European Research Council (ERC) advanced grant (FP/2007-2013/ERC grant 2012-322698), a Netherlands Organization for Scientific Research (NWO) Spinoza prize (NWO SPI 92-266) and the Stiftelsen Kristian Gerhard Jebsen foundation (Norway). A.Z. holds a Rosalind Franklin Fellowship (University of Groningen), ERC starting grant (715772) and NWO Vidi grant (178.056). J.F. is funded by an NWO Vidi grant (NWO-VIDI 864.13.013). A.Z. and J.F. are also funded by CardioVasculair Onderzoek Nederland (CVON 2012-03).

Publisher Copyright:
© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

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Rothschild, D., Weissbrod, O., Barkan, E., Kurilshikov, A., Korem, T., Zeevi, D., Costea, P. I., Godneva, A., Kalka, I. N., Bar, N., Shilo, S., Lador, D., Vila, A. V., Zmora, N., Pevsner-Fischer, M., Israeli, D., Kosower, N., Malka, G., Wolf, B. C., ... Segal, E. (2018). Environment dominates over host genetics in shaping human gut microbiota. Nature, 555(7695), 210-215. https://doi.org/10.1038/nature25973

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title = "Environment dominates over host genetics in shaping human gut microbiota",

abstract = "Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.",

author = "Daphna Rothschild and Omer Weissbrod and Elad Barkan and Alexander Kurilshikov and Tal Korem and David Zeevi and Costea, {Paul I.} and Anastasia Godneva and Kalka, {Iris N.} and Noam Bar and Smadar Shilo and Dar Lador and Vila, {Arnau Vich} and Niv Zmora and Meirav Pevsner-Fischer and David Israeli and Noa Kosower and Gal Malka and Wolf, {Bat Chen} and Tali Avnit-Sagi and Maya Lotan-Pompan and Adina Weinberger and Zamir Halpern and Shai Carmi and Jingyuan Fu and Cisca Wijmenga and Alexandra Zhernakova and Eran Elinav and Eran Segal",

note = "Funding Information: The project was provided by the Wellcome Trust under awards 076113 and 085475. E.S. is supported by the Crown Human Genome Center; the Else Kroener Fresenius Foundation; D. L. Schwarz; J. N. Halpern; L. Steinberg; and grants funded by the European Research Council and the Israel Science Foundation. E.E. is supported by Y. and R. Ungar, the Gurwin Family Fund for Scientific Research, the Leona M. and Harry B. Helmsley Charitable Trust, the Israel Science Foundation and the Helmholtz Foundation. E.E. holds the Sir Marc and Lady Tania Feldmann Professorial Chair in Immunology, is a senior fellow of the Canadian Institute for Advanced Research, and is an international scholar at the Bill and Melinda Gates Foundation and Howard Hughes Medical Institute. D.R. received a Levi Eshkol PhD Scholarship for Personalized Medicine by the Israeli Ministry of Science. LLD was made possible by grants from the Top Institute Food and Nutrition (GH001) to C.W. C.W. is funded by a European Research Council (ERC) advanced grant (FP/2007-2013/ERC grant 2012-322698), a Netherlands Organization for Scientific Research (NWO) Spinoza prize (NWO SPI 92-266) and the Stiftelsen Kristian Gerhard Jebsen foundation (Norway). A.Z. holds a Rosalind Franklin Fellowship (University of Groningen), ERC starting grant (715772) and NWO Vidi grant (178.056). J.F. is funded by an NWO Vidi grant (NWO-VIDI 864.13.013). A.Z. and J.F. are also funded by CardioVasculair Onderzoek Nederland (CVON 2012-03). Publisher Copyright: {\textcopyright} 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",

year = "2018",

month = mar,

day = "8",

doi = "10.1038/nature25973",

language = "American English",

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Rothschild, D, Weissbrod, O, Barkan, E, Kurilshikov, A, Korem, T, Zeevi, D, Costea, PI, Godneva, A, Kalka, IN, Bar, N, Shilo, S, Lador, D, Vila, AV, Zmora, N, Pevsner-Fischer, M, Israeli, D, Kosower, N, Malka, G, Wolf, BC, Avnit-Sagi, T, Lotan-Pompan, M, Weinberger, A, Halpern, Z, Carmi, S, Fu, J, Wijmenga, C, Zhernakova, A, Elinav, E & Segal, E 2018, 'Environment dominates over host genetics in shaping human gut microbiota', Nature, vol. 555, no. 7695, pp. 210-215. https://doi.org/10.1038/nature25973

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T1 - Environment dominates over host genetics in shaping human gut microbiota

AU - Rothschild, Daphna

AU - Weissbrod, Omer

AU - Barkan, Elad

AU - Kurilshikov, Alexander

AU - Korem, Tal

AU - Zeevi, David

AU - Costea, Paul I.

AU - Godneva, Anastasia

AU - Kalka, Iris N.

AU - Bar, Noam

AU - Shilo, Smadar

AU - Lador, Dar

AU - Vila, Arnau Vich

AU - Zmora, Niv

AU - Pevsner-Fischer, Meirav

AU - Israeli, David

AU - Kosower, Noa

AU - Malka, Gal

AU - Wolf, Bat Chen

AU - Avnit-Sagi, Tali

AU - Lotan-Pompan, Maya

AU - Weinberger, Adina

AU - Halpern, Zamir

AU - Carmi, Shai

AU - Fu, Jingyuan

AU - Wijmenga, Cisca

AU - Zhernakova, Alexandra

AU - Elinav, Eran

AU - Segal, Eran

N1 - Funding Information: The project was provided by the Wellcome Trust under awards 076113 and 085475. E.S. is supported by the Crown Human Genome Center; the Else Kroener Fresenius Foundation; D. L. Schwarz; J. N. Halpern; L. Steinberg; and grants funded by the European Research Council and the Israel Science Foundation. E.E. is supported by Y. and R. Ungar, the Gurwin Family Fund for Scientific Research, the Leona M. and Harry B. Helmsley Charitable Trust, the Israel Science Foundation and the Helmholtz Foundation. E.E. holds the Sir Marc and Lady Tania Feldmann Professorial Chair in Immunology, is a senior fellow of the Canadian Institute for Advanced Research, and is an international scholar at the Bill and Melinda Gates Foundation and Howard Hughes Medical Institute. D.R. received a Levi Eshkol PhD Scholarship for Personalized Medicine by the Israeli Ministry of Science. LLD was made possible by grants from the Top Institute Food and Nutrition (GH001) to C.W. C.W. is funded by a European Research Council (ERC) advanced grant (FP/2007-2013/ERC grant 2012-322698), a Netherlands Organization for Scientific Research (NWO) Spinoza prize (NWO SPI 92-266) and the Stiftelsen Kristian Gerhard Jebsen foundation (Norway). A.Z. holds a Rosalind Franklin Fellowship (University of Groningen), ERC starting grant (715772) and NWO Vidi grant (178.056). J.F. is funded by an NWO Vidi grant (NWO-VIDI 864.13.013). A.Z. and J.F. are also funded by CardioVasculair Onderzoek Nederland (CVON 2012-03). Publisher Copyright: © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

PY - 2018/3/8

Y1 - 2018/3/8

N2 - Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

AB - Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

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VL - 555

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JO - Nature

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Environment dominates over host genetics in shaping human gut microbiota

Abstract

Bibliographical note

UN SDGs

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