Gut microbes modulate (p)ppGpp during a time-restricted feeding regimen.
Gut microbes modulate (p)ppGpp during a time-restricted feeding regimen.
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作者：
哺乳动物表现出的日常禁食和进食模式会在肠道内产生波动的环境。通过用多形拟杆菌定植无菌小鼠，并通过时间限制的喂养周期检查基因表达，我们证明了这种突出的肠道共生体表现出严格反应的基因表达模式特征，并在喂养方案的宿主禁食阶段增加了 ppGpp 水平。无法产生 (p)ppGpp 的突变体无法产生这种转录反应，表现出不受限制的染色体复制，并且无法在宿主禁食阶段维持种群规模。此外，B. thetaiotaomicron 需要 (p)ppGpp 在体外和体内利用宿主聚糖，而无法产生 (p)ppGpp 的突变体在宿主禁食阶段的粘液层定植中表现出缺陷。小鼠和人类的完整肠道微生物群落也以这种方式增加 ppGpp 水平，表明这种反应似乎在物种间普遍存在，并且在哺乳动物肠道群落中保守。总之，这些结果确定了一种细胞内信号，使肠道微生物能够将其生理学与其宿主的限时喂养方案相协调。哺乳动物不会连续进食，而是将进食集中在一天中有限的时间内。这种行为使哺乳动物肠道微生物群呈现出波动的环境，从而对宿主-微生物群相互作用、感染风险、免疫反应、药物代谢和健康的其他方面产生影响。我们证明，在小鼠中，在限时喂养方案的禁食阶段，肠道微生物会升高细胞内信号分子 (p)ppGpp 的水平。在具有代表性的人类肠道共生物种中禁用这种反应可显着减少宿主禁食阶段的定植。这种反应似乎是跨物种普遍存在的，并且在哺乳动物肠道群落中是保守的，这突显了健康肠道微生物组在不稳定环境中保持稳定性的途径。
Mammals exhibit daily fasting and feeding patterns that produce a fluctuating environment in the gut. By colonizing germfree mice with Bacteroides thetaiotaomicron and examining gene expression through a time-restricted feeding cycle, we demonstrate that this prominent gut commensal exhibits gene expression patterns characteristic of a stringent response and increases ppGpp levels during the host-fasting phase of the feeding regimen. Mutants unable to produce (p)ppGpp fail to produce this transcriptional response, exhibit unrestrained chromosomal replication, and cannot maintain population size during the host-fasting phase. Additionally, B. thetaiotaomicron requires (p)ppGpp to utilize host glycans both in vitro and in vivo, and mutants unable to produce (p)ppGpp display deficiencies in mucus layer colonization during the host-fasting phase. Complete gut microbial communities from mice and humans also increase ppGpp levels in this manner, demonstrating that this response appears to be general across species and conserved across mammalian gut communities. Together, these results identify an intracellular signal that allows gut microbes to coordinate their physiology with a time-restricted feeding regimen of their host. Mammals do not eat continuously, instead concentrating their feeding to a restricted portion of the day. This behavior presents the mammalian gut microbiota with a fluctuating environment with consequences for host-microbiome interaction, infection risk, immune response, drug metabolism, and other aspects of health. We demonstrate that in mice, gut microbes elevate levels of an intracellular signaling molecule, (p)ppGpp, during the fasting phase of a time-restricted feeding regimen. Disabling this response in a representative human gut commensal species significantly reduces colonization during this host-fasting phase. This response appears to be general across species and conserved across mammalian gut communities, highlighting a pathway that allows healthy gut microbiomes to maintain stability in an unstable environment.
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DOI：
10.1038/nrmicro3552
发表时间：
2016-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Donaldson GP;Lee SM;Mazmanian SK
通讯作者：
Mazmanian SK
影响因子：
64.8
作者：
Glenwright AJ;Pothula KR;Bhamidimarri SP;Chorev DS;Baslé A;Firbank SJ;Zheng H;Robinson CV;Winterhalter M;Kleinekathöfer U;Bolam DN;van den Berg B
通讯作者：
van den Berg B
影响因子：
16.6
作者：
Germain, Elsa;Guiraud, Paul;Maisonneuve, Etienne
通讯作者：
Maisonneuve, Etienne
影响因子：
6.9
作者：
Hutchison, Amy T.;Regmi, Prashant;Heilbronn, Leonie K.
通讯作者：
Heilbronn, Leonie K.
影响因子：
4.4
作者：
Brockmann-Gretza O;Kalinowski J
通讯作者：
Kalinowski J