Department of Child Health and Child Health Research Institute, Faculty of Medicine, University of Missouri, Columbia, MO 65201, United States.
Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, United States; University of Missouri, Metagenomics Center, Columbia, MO, United States.
Exp Neurol. 2020 Dec;334:113439. doi: 10.1016/j.expneurol.2020.113439. Epub 2020 Aug 22.
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/6 J mice to IH or room air (RA) for 6 weeks, and fecal matter was collected and frozen. C57Bl/6 J 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 16 s 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.
阻塞性睡眠呼吸暂停（OSA）是一种慢性流行疾病，其特征为间歇性低氧（IH）和睡眠碎片化（SF）。有证据表明，OSA 可能改变肠道微生物组（GM）的多样性和组成，从而促进一些与 OSA 相关的疾病的发生。然而，目前尚不清楚 IH 引起的 GM 紊乱是否会引起睡眠障碍，而这些睡眠障碍是 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 C57Bl/6J 小鼠暴露于 IH 或室内空气（RA）中 6 周，收集并冷冻粪便。然后，将 C57Bl/6J 未处理的小鼠随机分配到粪便微生物群转移（FMT）方案中，进行 3 周的 IH 或 RA 粪便混悬液处理，然后使用 16s rRNA 测序分析其 GM。此外，FMT 受者使用压电方法进行连续 3 天的睡眠记录。正如预期的那样，FMT-IH 和 FMT-RA 小鼠表现出不同的分类群谱，这与 IH 对 GM 的先前影响相对应。此外，FMT-IH 小鼠在暗周期表现出睡眠时间增加和更长的睡眠阶段频率增加，表明嗜睡增加（p<0.0001 与 FMT-RA 小鼠相比）。因此，IH 暴露引起的 GM 多样性改变可以在没有并发 IH 的情况下引起睡眠障碍，这表明睡眠障碍至少部分可以由 IH 引起的 GM 改变介导。
