title: Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations.
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.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Thaiss
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Maayan
authors.initials: M
authors.lastname: Levy
authors.affiliation: 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.
authors.forename: Tal
authors.initials: T
authors.lastname: Korem
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Lenka
authors.initials: L
authors.lastname: Dohnalová
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Shapiro
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Jaitin
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: David
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Winter
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Meital
authors.initials: M
authors.lastname: Gury-BenAri
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Tatirovsky
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Timur
authors.initials: T
authors.lastname: Tuganbaev
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Federici
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Niv
authors.initials: N
authors.lastname: Zmora
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Zeevi
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Mally
authors.initials: M
authors.lastname: Dori-Bachash
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Meirav
authors.initials: M
authors.lastname: Pevsner-Fischer
authors.affiliation: Electron Microscopy Unit, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Kartvelishvily
authors.affiliation: Targeted Metabolomics Unit, Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Brandis
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Harmelin
authors.affiliation: 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.
authors.forename: Oren
authors.initials: O
authors.lastname: Shibolet
authors.affiliation: 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.
authors.forename: Zamir
authors.initials: Z
authors.lastname: Halpern
authors.affiliation: 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.
authors.forename: Kenya
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.affiliation: 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.
authors.forename: Eran
authors.initials: E
authors.lastname: Segal
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: eran.elinav@weizmann.ac.il.
authors.forename: Eran
authors.initials: E
authors.lastname: Elinav
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D002940:Circadian Rhythm; D003106:Colon / Q000378:metabolism / Q000382:microbiology*; D000069196:Gastrointestinal Microbiome; D005856:Germ-Free Life; D008099:Liver / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D059467:Transcriptome
chemical_list: D002843:Chromatin
keywords: biogeography; chronopharmacology; circadian clock; diurnal rhythm; metabolome; metagenome; microbiome; transcriptome