Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations

Christoph A. Thaiss; Maayan Levy; Tal Korem; Lenka Dohnalová; Hagit Shapiro; Diego A. Jaitin; Eyal David; Deborah R. Winter; Meital Gury-BenAri; Evgeny Tatirovsky; Timur Tuganbaev; Sara Federici; Niv Zmora; David Zeevi; Mally Dori-Bachash; Meirav Pevsner-Fischer; Elena Kartvelishvily; Alexander Brandis; Alon Harmelin; Oren Shibolet; Zamir Halpern; Kenya Honda; Ido Amit; Eran Segal; Eran Elinav

doi:10.1016/j.cell.2016.11.003

Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations

Christoph A. Thaiss, Maayan Levy, Tal Korem, Lenka Dohnalová, Hagit Shapiro, Diego A. Jaitin, Eyal David, Deborah R. Winter, Meital Gury-BenAri, Evgeny Tatirovsky, Timur Tuganbaev, Sara Federici, Niv Zmora, David Zeevi, Mally Dori-Bachash, Meirav Pevsner-Fischer, Elena Kartvelishvily, Alexander Brandis, Alon Harmelin, Oren ShiboletZamir Halpern, Kenya Honda, Ido Amit, Eran Segal, Eran Elinav

Department of Microbiology and Immunology

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

467 Citations (Scopus)

Abstract

The intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis, but the mechanisms by which the rhythmic microbiota influences host circadian activity remain elusive. Using integrated multi-omics and imaging approaches, we demonstrate that the gut microbiota features oscillating biogeographical localization and metabolome patterns that determine the rhythmic exposure of the intestinal epithelium to different bacterial species and their metabolites over the course of a day. This diurnal microbial behavior drives, in turn, the global programming of the host circadian transcriptional, epigenetic, and metabolite oscillations. Surprisingly, disruption of homeostatic microbiome rhythmicity not only abrogates normal chromatin and transcriptional oscillations of the host, but also incites genome-wide de novo oscillations in both intestine and liver, thereby impacting diurnal fluctuations of host physiology and disease susceptibility. As such, the rhythmic biogeography and metabolome of the intestinal microbiota regulates the temporal organization and functional outcome of host transcriptional and epigenetic programs.

Original language	English
Pages (from-to)	1495-1510.e12
Journal	Cell
Volume	167
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2016.11.003
Publication status	Published - 2016 Dec 1

Keywords

biogeography
chronopharmacology
circadian clock
diurnal rhythm
metabolome
metagenome
microbiome
transcriptome

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

Access to Document

10.1016/j.cell.2016.11.003

Cite this

Thaiss, C. A., Levy, M., Korem, T., Dohnalová, L., Shapiro, H., Jaitin, D. A., David, E., Winter, D. R., Gury-BenAri, M., Tatirovsky, E., Tuganbaev, T., Federici, S., Zmora, N., Zeevi, D., Dori-Bachash, M., Pevsner-Fischer, M., Kartvelishvily, E., Brandis, A., Harmelin, A., ... Elinav, E. (2016). Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations. Cell, 167(6), 1495-1510.e12. https://doi.org/10.1016/j.cell.2016.11.003

Thaiss, CA, Levy, M, Korem, T, Dohnalová, L, Shapiro, H, Jaitin, DA, David, E, Winter, DR, Gury-BenAri, M, Tatirovsky, E, Tuganbaev, T, Federici, S, Zmora, N, Zeevi, D, Dori-Bachash, M, Pevsner-Fischer, M, Kartvelishvily, E, Brandis, A, Harmelin, A, Shibolet, O, Halpern, Z, Honda, K, Amit, I, Segal, E & Elinav, E 2016, 'Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations', Cell, vol. 167, no. 6, pp. 1495-1510.e12. https://doi.org/10.1016/j.cell.2016.11.003

@article{f923d16ad1fc4b458a910fce93b121d8,

title = "Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations",

abstract = "The intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis, but the mechanisms by which the rhythmic microbiota influences host circadian activity remain elusive. Using integrated multi-omics and imaging approaches, we demonstrate that the gut microbiota features oscillating biogeographical localization and metabolome patterns that determine the rhythmic exposure of the intestinal epithelium to different bacterial species and their metabolites over the course of a day. This diurnal microbial behavior drives, in turn, the global programming of the host circadian transcriptional, epigenetic, and metabolite oscillations. Surprisingly, disruption of homeostatic microbiome rhythmicity not only abrogates normal chromatin and transcriptional oscillations of the host, but also incites genome-wide de novo oscillations in both intestine and liver, thereby impacting diurnal fluctuations of host physiology and disease susceptibility. As such, the rhythmic biogeography and metabolome of the intestinal microbiota regulates the temporal organization and functional outcome of host transcriptional and epigenetic programs.",

keywords = "biogeography, chronopharmacology, circadian clock, diurnal rhythm, metabolome, metagenome, microbiome, transcriptome",

author = "Thaiss, {Christoph A.} and Maayan Levy and Tal Korem and Lenka Dohnalov{\'a} and Hagit Shapiro and Jaitin, {Diego A.} and Eyal David and Winter, {Deborah R.} and Meital Gury-BenAri and Evgeny Tatirovsky and Timur Tuganbaev and Sara Federici and Niv Zmora and David Zeevi and Mally Dori-Bachash and Meirav Pevsner-Fischer and Elena Kartvelishvily and Alexander Brandis and Alon Harmelin and Oren Shibolet and Zamir Halpern and Kenya Honda and Ido Amit and Eran Segal and Eran Elinav",

note = "Funding Information: We thank the members of the E.E. and E.S. labs for discussions and Ilan Rosenshine for sharing important tools. We acknowledge Ziv Zwighaft and Gad Asher for providing polyamine-deficient animal diet and helpful advice, and Tevie Mehlman, Carmit Bar-Nathan, Osnat Amram, as well as the Weizmann Histology Unit for technical support. C.A.T. received a Boehringer Ingelheim Fonds PhD Fellowship and thanks Shalev Itzkovitz and Yair Raisner for insightful discussions. T.K. is supported by the Ministry of Science, Technology & Space, Israel. N.Z. is supported by the Gilead Sciences International Research Scholars Program in Liver Disease. K.H. is supported by CREST, Japan Agency for Medical Research and Development. E.S. is supported by the Crown Human Genome Center; the Else Kroener Fresenius Foundation; Donald L. Schwarz, Sherman Oaks, CA; Jack N. Halpern, New York, NY; Leesa Steinberg, Canada; and grants funded by the European Research Council and the Israel Science Foundation. E.E. is supported by Yael and Rami Ungar, Israel; Leona M. and Harry B. Helmsley Charitable Trust; the Gurwin Family Fund for Scientific Research; Crown Endowment Fund for Immunological Research; estate of Jack Gitlitz; estate of Lydia Hershkovich; the Benoziyo Endowment Fund for the Advancement of Science; Adelis Foundation; John L. and Vera Schwartz, Pacific Palisades; Alan Markovitz, Canada; Cynthia Adelson, Canada; CNRS (Centre National de la Recherche Scientifique); estate of Samuel and Alwyn J. Weber; Mr. and Mrs. Donald L. Schwarz, Sherman Oaks; grants funded by the European Research Council; the German-Israel Binational Foundation; the Israel Science Foundation; the Minerva Foundation; the Rising Tide Foundation; and the Alon Foundation scholar award. E.E. is the incumbent of the Rina Gudinski Career Development Chair and a senior fellow of the Canadian Institute For Advanced Research (CIFAR). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = dec,

day = "1",

doi = "10.1016/j.cell.2016.11.003",

language = "English",

volume = "167",

pages = "1495--1510.e12",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations

AU - Thaiss, Christoph A.

AU - Levy, Maayan

AU - Korem, Tal

AU - Dohnalová, Lenka

AU - Shapiro, Hagit

AU - Jaitin, Diego A.

AU - David, Eyal

AU - Winter, Deborah R.

AU - Gury-BenAri, Meital

AU - Tatirovsky, Evgeny

AU - Tuganbaev, Timur

AU - Federici, Sara

AU - Zmora, Niv

AU - Zeevi, David

AU - Dori-Bachash, Mally

AU - Pevsner-Fischer, Meirav

AU - Kartvelishvily, Elena

AU - Brandis, Alexander

AU - Harmelin, Alon

AU - Shibolet, Oren

AU - Halpern, Zamir

AU - Honda, Kenya

AU - Amit, Ido

AU - Segal, Eran

AU - Elinav, Eran

N1 - Funding Information: We thank the members of the E.E. and E.S. labs for discussions and Ilan Rosenshine for sharing important tools. We acknowledge Ziv Zwighaft and Gad Asher for providing polyamine-deficient animal diet and helpful advice, and Tevie Mehlman, Carmit Bar-Nathan, Osnat Amram, as well as the Weizmann Histology Unit for technical support. C.A.T. received a Boehringer Ingelheim Fonds PhD Fellowship and thanks Shalev Itzkovitz and Yair Raisner for insightful discussions. T.K. is supported by the Ministry of Science, Technology & Space, Israel. N.Z. is supported by the Gilead Sciences International Research Scholars Program in Liver Disease. K.H. is supported by CREST, Japan Agency for Medical Research and Development. E.S. is supported by the Crown Human Genome Center; the Else Kroener Fresenius Foundation; Donald L. Schwarz, Sherman Oaks, CA; Jack N. Halpern, New York, NY; Leesa Steinberg, Canada; and grants funded by the European Research Council and the Israel Science Foundation. E.E. is supported by Yael and Rami Ungar, Israel; Leona M. and Harry B. Helmsley Charitable Trust; the Gurwin Family Fund for Scientific Research; Crown Endowment Fund for Immunological Research; estate of Jack Gitlitz; estate of Lydia Hershkovich; the Benoziyo Endowment Fund for the Advancement of Science; Adelis Foundation; John L. and Vera Schwartz, Pacific Palisades; Alan Markovitz, Canada; Cynthia Adelson, Canada; CNRS (Centre National de la Recherche Scientifique); estate of Samuel and Alwyn J. Weber; Mr. and Mrs. Donald L. Schwarz, Sherman Oaks; grants funded by the European Research Council; the German-Israel Binational Foundation; the Israel Science Foundation; the Minerva Foundation; the Rising Tide Foundation; and the Alon Foundation scholar award. E.E. is the incumbent of the Rina Gudinski Career Development Chair and a senior fellow of the Canadian Institute For Advanced Research (CIFAR). Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - The intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis, but the mechanisms by which the rhythmic microbiota influences host circadian activity remain elusive. Using integrated multi-omics and imaging approaches, we demonstrate that the gut microbiota features oscillating biogeographical localization and metabolome patterns that determine the rhythmic exposure of the intestinal epithelium to different bacterial species and their metabolites over the course of a day. This diurnal microbial behavior drives, in turn, the global programming of the host circadian transcriptional, epigenetic, and metabolite oscillations. Surprisingly, disruption of homeostatic microbiome rhythmicity not only abrogates normal chromatin and transcriptional oscillations of the host, but also incites genome-wide de novo oscillations in both intestine and liver, thereby impacting diurnal fluctuations of host physiology and disease susceptibility. As such, the rhythmic biogeography and metabolome of the intestinal microbiota regulates the temporal organization and functional outcome of host transcriptional and epigenetic programs.

AB - The intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis, but the mechanisms by which the rhythmic microbiota influences host circadian activity remain elusive. Using integrated multi-omics and imaging approaches, we demonstrate that the gut microbiota features oscillating biogeographical localization and metabolome patterns that determine the rhythmic exposure of the intestinal epithelium to different bacterial species and their metabolites over the course of a day. This diurnal microbial behavior drives, in turn, the global programming of the host circadian transcriptional, epigenetic, and metabolite oscillations. Surprisingly, disruption of homeostatic microbiome rhythmicity not only abrogates normal chromatin and transcriptional oscillations of the host, but also incites genome-wide de novo oscillations in both intestine and liver, thereby impacting diurnal fluctuations of host physiology and disease susceptibility. As such, the rhythmic biogeography and metabolome of the intestinal microbiota regulates the temporal organization and functional outcome of host transcriptional and epigenetic programs.

KW - biogeography

KW - chronopharmacology

KW - circadian clock

KW - diurnal rhythm

KW - metabolome

KW - metagenome

KW - microbiome

KW - transcriptome

UR - http://www.scopus.com/inward/record.url?scp=85000363137&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85000363137&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2016.11.003

DO - 10.1016/j.cell.2016.11.003

M3 - Article

C2 - 27912059

AN - SCOPUS:85000363137

SN - 0092-8674

VL - 167

SP - 1495-1510.e12

JO - Cell

JF - Cell

IS - 6

ER -

Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this