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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)1495-1510.e12
JournalCell
Volume167
Issue number6
DOIs
StatePublished - 1 Dec 2016

Funding

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

    Keywords

    • biogeography
    • chronopharmacology
    • circadian clock
    • diurnal rhythm
    • metabolome
    • metagenome
    • microbiome
    • transcriptome

    Fingerprint

    Dive into the research topics of 'Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations'. Together they form a unique fingerprint.

    Cite this