Li Lingyue, Meng Zilin, Huang Yuebing, Xu Luyao, Chen Qianling, Qiao Dongfang, Yue Xia
Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China.
Biomedicines. 2024 Nov 21;12(12):2654. doi: 10.3390/biomedicines12122654.
Chronic sleep deprivation (CSD) plays an important role in mood disorders. However, the changes in the gut microbiota and metabolites associated with CSD-induced anxiety/depression-like behavior in female mice have not been determined. Due to the influence of endogenous hormone levels, females are more susceptible than males to negative emotions caused by sleep deprivation. Here, we aim to investigate how CSD changes the gut microbiota and behavior and uncover the relationship between CSD and gut microbiota and its metabolites in female mice.
We used a 48-day sleep deprivation (SD) model using the modified multiple platform method (MMPM) to induce anxiety/depression-like behavior in female C57BL/6J mice and verified our results using the open field test, elevated plus maze, novel object recognition test, forced swim test, and tail suspension test. We collected fecal samples of mice for 16S rDNA sequencing and untargeted metabolomic analysis and colons for histopathological observation. We used Spearmen analysis to find the correlations between differential bacterial taxa, fecal metabolites, and behaviors.
Our study demonstrates that CSD induced anxiety/depressive-like behaviors in female mice. The results of 16S rDNA sequencing suggested that the relative abundance of the harmful bacteria , , , and were significantly increased, while the beneficial bacteria , , and were significantly decreased after SD. Glycerophospholipid metabolism and glutathione metabolism were identified as key pathways in the fecal metabolism related to oxidative stress and inflammatory states of the intestine. Histological observation showed hyperplasia of epithelial cells, a decrease in goblet cells, and glandular atrophy of the colon in SD mice. There were correlations between some of the differential bacterial taxa, fecal metabolites, and behaviors.
In summary, we found that CSD induced anxiety/depression-like behavior, caused gut microbiota dysbiosis, altered fecal metabolism, and damaged the colon barrier in female mice.
慢性睡眠剥夺（CSD）在情绪障碍中起重要作用。然而，与雌性小鼠CSD诱导的焦虑/抑郁样行为相关的肠道微生物群和代谢物的变化尚未确定。由于内源性激素水平的影响，雌性比雄性更容易受到睡眠剥夺引起的负面情绪的影响。在此，我们旨在研究CSD如何改变肠道微生物群和行为，并揭示雌性小鼠中CSD与肠道微生物群及其代谢物之间的关系。
我们使用改良多平台法（MMPM）的48天睡眠剥夺（SD）模型诱导雌性C57BL/6J小鼠出现焦虑/抑郁样行为，并使用旷场试验、高架十字迷宫、新物体识别试验、强迫游泳试验和悬尾试验验证我们的结果。我们收集小鼠粪便样本进行16S rDNA测序和非靶向代谢组学分析，并收集结肠进行组织病理学观察。我们使用Spearmen分析来寻找差异细菌分类群、粪便代谢物和行为之间的相关性。
我们的研究表明，CSD在雌性小鼠中诱导了焦虑/抑郁样行为。16S rDNA测序结果表明，SD后有害细菌、、和的相对丰度显著增加，而有益细菌、和显著减少。甘油磷脂代谢和谷胱甘肽代谢被确定为与肠道氧化应激和炎症状态相关的粪便代谢中的关键途径。组织学观察显示，SD小鼠上皮细胞增生、杯状细胞减少和结肠腺体萎缩。一些差异细菌分类群、粪便代谢物和行为之间存在相关性。
总之，我们发现CSD诱导了焦虑/抑郁样行为，导致肠道微生物群失调，改变了粪便代谢，并损害了雌性小鼠的结肠屏障。
