Fecal microbiota transplantation from mice exposed to chronic intermittent hypoxia elicits sleep disturbances in naïve mice.

Fecal microbiota transplantation from mice exposed to chronic intermittent hypoxia elicits sleep disturbances in naïve mice.
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DOI:
10.1016/j.expneurol.2020.113439
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发表时间:
2020-12
影响因子:
5.3
通讯作者:
Gozal D
Gozal D
中科院分区:
医学2区
文献类型:
--
作者:
Badran M;Khalyfa A;Ericsson A;Gozal D

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阻塞性睡眠呼吸暂停(OSA)是一种以间歇性缺氧(IH)和睡眠片段化(SF)为特征的慢性流行疾病。有证据表明,OSA可以改变肠道微生物组(GM)的多样性和组成,然后可能促进一些OSA相关疾病的发生。然而,目前尚不清楚IH引起的GM扰动是否会引起睡眠障碍,这是IH暴露小鼠睡眠倾向增加的基础。为了评估这个问题,我们将C57 Bl/6 J小鼠暴露于IH或室内空气(RA)6周,并收集粪便并冷冻。然后将C57 Bl/6 J未处理小鼠随机分配至粪便微生物群转移(FMT)方案,持续3周,使用IH或RA粪便涂片,然后使用16 s rRNA测序分析其GM。此外,FMT接受者连续3天使用压电方法进行睡眠记录。正如预期的那样,FMT-IH和FMT-RA小鼠表现出不同的分类特征,这与IH对GM的先前影响相对应。此外,FMT-IH小鼠在黑暗周期期间表现出增加的睡眠持续时间和较长睡眠发作的频率,表明增加的嗜睡(p<0.0001相对于FMT-RA小鼠)。因此,IH暴露诱导的GM多样性的改变可以在没有并发IH的情况下引起睡眠障碍,这表明睡眠障碍可以介导,至少部分地,由IH诱导的GM改变。
Obstructive sleep apnea (OSA) is a chronic prevalent condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). Evidence suggests that OSA can alter the gut microbiome (GM) diversity and composition that may then promote the occurrence of some of the OSA-associated morbidities. However, it is unclear whether perturbations in the GM caused by IH can elicit sleep disturbances that underlie the increased sleep propensity that occurs in IH-exposed mice. To evaluate this issue, we exposed C57Bl/6J mice to IH or room air (RA) for 6 weeks, and fecal matter was collected and frozen. C57Bl/6J naïve mice were then randomly assigned to a fecal microbiota transfer (FMT) protocol for 3 weeks with either IH or RA fecal slur, and their GM was then analyzed using 16s rRNA sequencing. In addition, FMT recipients underwent sleep recordings using piezoelectric approaches for 3 consecutive days. As anticipated, FMT-IH and FMT-RA mice showed different taxonomic profiles that corresponded to previous effects of IH on GM. Furthermore, FMT-IH mice exhibited increased sleep duration and the frequency of longer sleep bouts during the dark cycle, suggesting increased sleepiness (p<0.0001 vs. FMT-RA mice). Thus, alterations of GM diversity induced by IH exposures can elicit sleep disturbances in the absence of concurrent IH, suggesting that sleep disturbances can be mediated, at least in part, by IH-induced alterations in GM.
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