Center for Chinese Medicine Therapy and Systems Biology, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Life Sci. 2019 May 15;225:88-97. doi: 10.1016/j.lfs.2019.04.006. Epub 2019 Apr 4.
Given the lasting impact of chronic paradoxical sleep deprivation (PSD) on behavior and organism metabolic alternations, along with the role of the microbiome in neurobehavioral development and metabolism, we sought to examine the relationship between the microbiota and chronic PSD-induced behavioral and metabolic changes.
Psychological status of 7-day PSD (7d-PSD) male rats was tested by behavioral method, serum inflammatory cytokines and hypothalamic-pituitary-adrenal (HPA) axis-related hormones. In addition, GC-MS based urine metabolomics and 16S rRNA gene sequencing approaches were applied to estimate the influences of chronic PSD on host metabolism and gut-microbiota. Furtherly, microbial functional prediction and Spearman's correlation analysis were implemented to manifest the relations between the differential urinary metabolites and gut microbiota.
7d-PSD rats displayed depression-like behavior, metabolic and microbial changes. By integrating differential gut bacteria with indicators of depression and differential metabolites, we found that the alterations of Akkermansia, Oscillospira, Ruminococcus, Parabacteroides, Aggregatibacter and Phascolarctobacterium were closely related to abnormalities of depression symptoms and inflammatory cytokines. These bacteria also had close connections with host energy metabolism concerning arginine and proline metabolism, glycine, serine and threonine metabolism, and glyoxylate and dicarboxylate metabolism, pyruvate metabolism, which overlapped with the results of 16S rRNA gene function annotation.
These data suggest that a specific situation of circadian disturbance, chronic PSD-induced alterations in gut microbiota and related host changes in metabolism may be the pathogenesis of depression.
鉴于慢性矛盾性睡眠剥夺（PSD）对行为和机体代谢改变的持久影响，以及微生物组在神经行为发育和代谢中的作用，我们试图研究微生物组与慢性 PSD 引起的行为和代谢变化之间的关系。
通过行为方法、血清炎症细胞因子和下丘脑-垂体-肾上腺（HPA）轴相关激素测试了 7 天 PSD（7d-PSD）雄性大鼠的心理状态。此外，还应用基于 GC-MS 的尿液代谢组学和 16S rRNA 基因测序方法来估计慢性 PSD 对宿主代谢和肠道微生物群的影响。进一步，进行了微生物功能预测和 Spearman 相关性分析，以展示差异尿代谢物与肠道微生物群之间的关系。
7d-PSD 大鼠表现出抑郁样行为、代谢和微生物变化。通过整合差异肠道细菌与抑郁指标和差异代谢物，我们发现 Akkermansia、Oscillospira、Ruminococcus、Parabacteroides、Aggregatibacter 和 Phascolarctobacterium 的改变与抑郁症状和炎症细胞因子的异常密切相关。这些细菌还与宿主能量代谢密切相关，涉及精氨酸和脯氨酸代谢、甘氨酸、丝氨酸和苏氨酸代谢以及乙醛酸和二羧酸代谢、丙酮酸代谢，这与 16S rRNA 基因功能注释的结果重叠。
这些数据表明，昼夜节律紊乱的特定情况、慢性 PSD 引起的肠道微生物群改变以及相关宿主代谢改变可能是抑郁症的发病机制。
