Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis

Christoph A. Thaiss, David Zeevi, Maayan Levy, Gili Zilberman-Schapira, Jotham Suez, Anouk C. Tengeler, Lior Abramson, Meirav N. Katz, Tal Korem, Niv Zmora, Yael Kuperman, Inbal Biton, Shlomit Gilad, Alon Harmelin, Hagit Shapiro, Zamir Halpern, Eran Segal, Eran Elinav*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)514-529
Number of pages16
JournalCell
Volume159
Issue number3
DOIs
StatePublished - 23 Oct 2014

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