TY - JOUR
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 - 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 - We thank the Segal and Elinav group members for discussions; J. Goodrich for sharing the processed twins microbiome data with us; and participants and staff of the LifeLines DEEP cohort for their collaboration. S.C. thanks the Abisch–Frenkel Foundation. This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for 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). Author Contributions D.R., O.W. and E.B. conceived the project, designed and conducted all analyses, interpreted the results, wrote the manuscript and are listed in random order. A.K., A.V.V., J.F., C.W. and A.Z. performed the analyses of the Dutch cohort and interpreted the results. T.K., D.Z. and A.W. designed protocols and supervised data collection. T.K., D.Z., P.I.C., A.G., I.N.K. and N.B. conducted microbiome analyses. S.S. and D.L. designed nutritional and drug databases. N.Z., M.P.-F, D.I. and Z.H. coordinated and supervised clinical aspects of data collection. N.K., G.M. and B.C.W. coordinated and designed data collection. T.A.-S., M.L.-P. and A.W. developed protocols and performed genotyping and microbiome sequencing. S.C. designed the genetic analyses. E.E. and E.S. conceived and directed the project and analyses, designed the analyses, interpreted the results and wrote the manuscript.
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.
UR - http://www.scopus.com/inward/record.url?scp=85043351358&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/nature25973
DO - https://doi.org/10.1038/nature25973
M3 - مقالة
C2 - 29489753
SN - 0028-0836
VL - 555
SP - 210
EP - 215
JO - Nature
JF - Nature
IS - 7695
ER -
