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Cell. 2016 Dec 1;167(6):1495-1510.e12. doi: 10.1016/j.cell.2016.11.003.

Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations.

Author information

1
Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
2
Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
3
Electron Microscopy Unit, Weizmann Institute of Science, Rehovot 7610001, Israel.
4
Targeted Metabolomics Unit, Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel.
5
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 7610001, Israel.
6
Sackler Faculty of Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel; Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel; Digestive Center, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel.
7
RIKEN Center for Integrative Medical Sciences (IMS), Tsurumi, Yokohama, Kanagawa 230-0045, Japan; Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.
8
Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: eran.segal@weizmann.ac.il.
9
Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: eran.elinav@weizmann.ac.il.

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

PMID:
27912059
DOI:
10.1016/j.cell.2016.11.003
[Indexed for MEDLINE]
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