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

Research output: Contribution to journalArticle

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

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Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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