title: Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis.
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.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Thaiss
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Zeevi
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Maayan
authors.initials: M
authors.lastname: Levy
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Gili
authors.initials: G
authors.lastname: Zilberman-Schapira
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Jotham
authors.initials: J
authors.lastname: Suez
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Anouk C
authors.initials: AC
authors.lastname: Tengeler
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Abramson
authors.affiliation: 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.
authors.forename: Meirav N
authors.initials: MN
authors.lastname: Katz
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Korem
authors.affiliation: 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.
authors.forename: Niv
authors.initials: N
authors.lastname: Zmora
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Kuperman
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Biton
authors.affiliation: The Nancy and Stephen Grand Israel National Center for Personalized Medicine (INCPM), Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Gilad
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Harmelin
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Shapiro
authors.affiliation: 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.
authors.forename: Zamir
authors.initials: Z
authors.lastname: Halpern
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Segal
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: eran.elinav@weizmann.ac.il.
authors.forename: Eran
authors.initials: E
authors.lastname: Elinav
mesh_terms: D000818:Animals; D057906:Circadian Clocks; D002940:Circadian Rhythm; D064806:Dysbiosis / Q000382:microbiology / Q000503:physiopathology; D005247:Feeding Behavior; D018149:Glucose Intolerance; D006706:Homeostasis; D006801:Humans; D020179:Jet Lag Syndrome / Q000503:physiopathology; D008659:Metabolic Diseases / Q000382:microbiology / Q000503:physiopathology; D051379:Mice; D064307:Microbiota; D009765:Obesity / Q000378:metabolism; D012890:Sleep