Journal
CELL
Volume 167, Issue 6, Pages 1495-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2016.11.003
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Funding
- Boehringer Ingelheim Fonds PhD Fellowship
- Ministry of Science, Technology Space, Israel
- Gilead Sciences International Research Scholars Program in Liver Disease
- CREST, Japan Agency for Medical Research and Development
- Crown Human Genome Center
- Else Kroener Fresenius Foundation
- European Research Council
- Israel Science Foundation
- Leona M. and Harry B. Helmsley Charitable Trust
- Gurwin Family Fund for Scientific Research
- Crown Endowment Fund for Immunological Research
- estate of Jack Gitlitz
- estate of Lydia Hershkovich
- Benoziyo Endowment Fund for the Advancement of Science
- Adelis Foundation
- CNRS (Centre National de la Recherche Scientifique)
- estate of Samuel and Alwyn J. Weber
- German-Israel Binational Foundation
- Minerva Foundation
- Rising Tide Foundation
- Alon Foundation scholar award
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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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