Microbiota Diumal Rhythmicity Programs Host Transcriptome Oscillations
Microbiota Diumal Rhythmicity Programs Host Transcriptome Oscillations
复制标题
DOI：
10.1016/j.cell.2016.11.003
复制
发表时间：
2016-12-01
期刊：
影响因子：
64.5
通讯作者：
Elinav, Eran
中科院分区：
文献类型：
--
作者：
Thaiss, Christoph A.;Levy, Maayan;Elinav, Eran
肠道微生物群经历昼夜组成和功能振荡，影响代谢动态平衡，但节律性微生物群影响宿主昼夜节律活动的机制仍然难以捉摸。使用集成的多组学和成像方法，我们证明了肠道微生物群具有振荡的地理定位和代谢组模式，这些模式决定了肠上皮细胞在一天中有节奏地暴露于不同的细菌物种及其代谢产物。这种昼夜微生物行为反过来驱动宿主昼夜转录、表观遗传和代谢物振荡的全局编程。令人惊讶的是，稳态微生物组节律性的破坏不仅消除了宿主的正常染色质和转录振荡，而且还引发了肠和肝脏中的全基因组从头振荡，从而影响宿主生理学和疾病易感性的昼夜波动。因此，肠道微生物群的节律性代谢和代谢组调节宿主转录和表观遗传程序的时间组织和功能结果。
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.