Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome
Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome
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DOI：
10.1371/journal.pone.0229001
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发表时间：
2020-02-20
期刊：
影响因子：
3.7
通讯作者：
Turek, Fred W.
中科院分区：
文献类型：
--
作者：
Bowers, Samuel J.;Vargas, Fernando;Turek, Fred W.
近年来已经确定，肠道微生物组可能通过影响宿主生理学的代谢物的改变在健康和疾病中发挥作用。虽然睡眠中断和肠道生态失调与许多相同的疾病有关，但在睡眠中断的背景下调查肠道微生物组的研究产生了不一致的结果，并且没有评估粪便代谢组。我们将小鼠暴露于5天的睡眠中断，然后进行4天的自由恢复睡眠，并使用16 S rRNA基因扩增子和非靶向LC-MS/MS质谱法在多个时间点评估粪便微生物组和粪便代谢组。我们发现，在恢复睡眠的第二天，睡眠中断组的微生物组和代谢组都发生了整体变化，当时大多数睡眠参数都恢复到了基线水平。我们观察到与对照小鼠相比，睡眠中断小鼠中厚壁菌门：拟杆菌门比率增加，沿着乳杆菌属、放线菌门和双歧杆菌属减少。后两个分类群在睡眠中断后的第四天仍然很低。我们还确定了多种类型的粪便代谢物，这些代谢物在睡眠中断的小鼠中含量不同，其中一些与生理学相关，并且通常受到微生物组的影响。这包括胆汁酸，微生物功能基因含量的推断表明睡眠中断小鼠中微生物胆盐水解酶基因的水平降低。总的来说，这项研究增加了将睡眠中断与肠道微生物组联系起来的证据基础，并将其扩展到粪便代谢组，确定了睡眠中断敏感的细菌分类群和代谢物类别，这些分类群可以作为治疗目标，以改善睡眠不良后的健康状况。
It has been established in recent years that the gut microbiome plays a role in health and disease, potentially via alterations in metabolites that influence host physiology. Although sleep disruption and gut dysbiosis have been associated with many of the same diseases, studies investigating the gut microbiome in the context of sleep disruption have yielded inconsistent results, and have not assessed the fecal metabolome. We exposed mice to five days of sleep disruption followed by four days of ad libitum recovery sleep, and assessed the fecal microbiome and fecal metabolome at multiple timepoints using 16S rRNA gene amplicons and untargeted LC-MS/MS mass spectrometry. We found global shifts in both the microbiome and metabolome in the sleep-disrupted group on the second day of recovery sleep, when most sleep parameters had recovered to baseline levels. We observed an increase in the Firmicutes:Bacteroidetes ratio, along with decreases in the genus Lactobacillus, phylum Actinobacteria, and genus Bifidobacterium in sleep-disrupted mice compared to control mice. The latter two taxa remained low at the fourth day post-sleep disruption. We also identified multiple classes of fecal metabolites that were differentially abundant in sleep-disrupted mice, some of which are physiologically relevant and commonly influenced by the microbiome. This included bile acids, and inference of microbial functional gene content suggested reduced levels of the microbial bile salt hydrolase gene in sleep-disrupted mice. Overall, this study adds to the evidence base linking disrupted sleep to the gut microbiome and expands it to the fecal metabolome, identifying sleep disruption-sensitive bacterial taxa and classes of metabolites that may serve as therapeutic targets to improve health after poor sleep.