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

^*Corresponding author for this work

Internal Medicine

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

633 Scopus citations

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
State	Published - 1 Dec 2016

Funding

Funders	Funder number
Rising Tide Foundation
Yael and Rami Ungar, Israel
Else Kröner-Fresenius-Stiftung
Israel Science Foundation
John L. and Vera Schwartz
German-Israel Binational Foundation
Benoziyo Endowment Fund for the Advancement of Science
Centre National de la Recherche Scientifique
Ministry of Science, Technology and Space
Gilead Sciences
Japan Agency for Medical Research and Development
Leona M. and Harry B. Helmsley Charitable Trust
Crown Human Genome Center
Core Research for Evolutional Science and Technology
Alcon Foundation
Crown Endowment Fund for Immunological Research
Lydia Hershkovich
Canadian Institute for Advanced Research
Minerva Foundation
European Research Council
Achelis Foundation
European Commission	615265

Keywords

biogeography
chronopharmacology
circadian clock
diurnal rhythm
metabolome
metagenome
microbiome
transcriptome

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10.1016/j.cell.2016.11.003

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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

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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.",

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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",

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year = "2016",

month = dec,

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

language = "אנגלית",

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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

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

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

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U2 - 10.1016/j.cell.2016.11.003

DO - 10.1016/j.cell.2016.11.003

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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

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