Microbiota Diumal Rhythmicity Programs Host Transcriptome Oscillations

被引：602

作者：

Thaiss, Christoph A. ^{[1
]}

Levy, Maayan ^{[1
]}

Korem, Tal ^{[2
,3
]}

Dohnalova, Lenka ^{[1
]}

Shapiro, Hagit ^{[1
]}

Jaitin, Diego A. ^{[1
]}

David, Eyal ^{[1
]}

Winter, Deborah R. ^{[1
]}

Gury-BenAri, Meital ^{[1
]}

Tatirovsky, Evgeny ^{[1
]}

Tuganbaev, Timur ^{[1
]}

Federici, Sara ^{[1
]}

Zmora, Niv ^{[1
]}

Zeevi, David ^{[2
,3
]}

Dori-Bachash, Mally ^{[1
]}

Pevsner-Fischer, Meirav ^{[1
]}

Kartvelishvily, Elena ^{[4
]}

Brandis, Alexander ^{[5
]}

Harmelin, Alon ^{[6
]}

Shibolet, Oren ^{[7
,8
,9
]}

Halpern, Zamir ^{[7
,8
,9
]}

Honda, Kenya ^{[10
,11
]}

Amit, Ido ^{[1
]}

Segal, Eran ^{[2
,3
]}

Elinav, Eran ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, IL-7610001 Rehovot, Israel

[2] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-7610001 Rehovot, Israel

[3] Weizmann Inst Sci, Dept Mol Cell Biol, IL-7610001 Rehovot, Israel

[4] Weizmann Inst Sci, Electron Microscopy Unit, IL-7610001 Rehovot, Israel

[5] Weizmann Inst Sci, Targeted Metabol Unit, Life Sci Core Facil, IL-7610001 Rehovot, Israel

[6] Weizmann Inst Sci, Dept Vet Resources, IL-7610001 Rehovot, Israel

[7] Tel Aviv Sourasky Med Ctr, Sackler Fac Med, IL-6423906 Tel Aviv, Israel

[8] Tel Aviv Sourasky Med Ctr, Res Ctr Digest Tract & Liver Dis, IL-6423906 Tel Aviv, Israel

[9] Tel Aviv Sourasky Med Ctr, Digest Ctr, IL-6423906 Tel Aviv, Israel

[10] RIKEN Ctr Integrat Med Sci IMS, Yokohama, Kanagawa 2300045, Japan

[11] Keio Univ, Dept Microbiol & Immunol, Sch Med, Shinjuku Ku, Tokyo 1608582, Japan

来源：

CELL | 2016年 / 167卷 / 06期

基金：

欧洲研究理事会; 以色列科学基金会;

关键词：

CIRCADIAN CLOCK; GENE-EXPRESSION; PROMOTES; TIME; ACETAMINOPHEN; METABOLISM; LANDSCAPE; ALIGNMENT; DRIVEN; CYCLE;

D O I：

10.1016/j.cell.2016.11.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：1495 / +

页数：28

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