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Cell. 2014 Oct 23;159(3):514-29. doi: 10.1016/j.cell.2014.09.048. Epub 2014 Oct 16.

Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis.

Author information

1
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
2
Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
3
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel; Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
4
Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Internal Medicine Department, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel; Digestive Center, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel.
5
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
6
The Nancy and Stephen Grand Israel National Center for Personalized Medicine (INCPM), Weizmann Institute of Science, Rehovot 76100, Israel.
7
Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Digestive Center, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel.
8
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: eran.elinav@weizmann.ac.il.

Abstract

All domains of life feature diverse molecular clock machineries that synchronize physiological processes to diurnal environmental fluctuations. However, no mechanisms are known to cross-regulate prokaryotic and eukaryotic circadian rhythms in multikingdom ecosystems. Here, we show that the intestinal microbiota, in both mice and humans, exhibits diurnal oscillations that are influenced by feeding rhythms, leading to time-specific compositional and functional profiles over the course of a day. Ablation of host molecular clock components or induction of jet lag leads to aberrant microbiota diurnal fluctuations and dysbiosis, driven by impaired feeding rhythmicity. Consequently, jet-lag-induced dysbiosis in both mice and humans promotes glucose intolerance and obesity that are transferrable to germ-free mice upon fecal transplantation. Together, these findings provide evidence of coordinated metaorganism diurnal rhythmicity and offer a microbiome-dependent mechanism for common metabolic disturbances in humans with aberrant circadian rhythms, such as those documented in shift workers and frequent flyers.

PMID:
25417104
DOI:
10.1016/j.cell.2014.09.048
[Indexed for MEDLINE]
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