Jiang Wenxia, Chen Jianjun, Gong Lei, Liu Fang, Zhao Huan, Yan Zhiwen, Li Yingli, Zhang Jie, Xiao Mi, Mu Jun
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No.1 Yixueyuan Road, Chongqing, China.
Institute of Life Sciences, Chongqing Medical University, No.1 Yixueyuan Road, Chongqing, China.
J Psychiatr Res. 2023 May;161:426-434. doi: 10.1016/j.jpsychires.2023.03.032. Epub 2023 Apr 4.
Post-stroke depression (PSD) is a common mental disorder of stroke survivors, its pathogenesis remains elusive. Previous studies suggested a role of the microbiota-gut-brain (MGB) axis in stroke and depression. In this study, we characterized microbial composition and function, and gut-brain metabolic signatures, in PSD rats. We aim to explore how disordered gut microbes participate in the pathogenesis of PSD through the MGB axis.
16S rRNA gene sequence and fecal metabolome analysis were performed to identify the gut microbiome and their functional metabolites in PSD rats. Then, the lipid metabolic signatures in the prefrontal cortex (PFC) of PSD were conducted by liquid chromatography mass spectrometry. Finally, the potential pathway between gut and brain in the onset of PSD were explored.
Compared to control and stroke rats, there were 10 genera (most of them belonged to phylum Firmicutes) significantly changed and 3 short chain fatty acids (SCFAs: butyric acid, acetic acid and pentanoic acid) significantly decreased in PSD rats. Meanwhile, altered gut microbial in PSD rats was significantly associated with these SCFAs. Compared with control and stroke rats, 57 lipid metabolites in the PFC of PSD rats were significantly changed. In addition, the altered SCFAs in PSD rats were also significantly correlated with most of disordered lipid metabolites in PFC.
Our findings suggest that the SCFAs may be a bridge of gut-brain communication. The Firmicutes-SCFAs-lipid metabolism might be a potential pathway to further investigate the MGB axis and pathogenesis of PSD.
卒中后抑郁(PSD)是卒中幸存者常见的精神障碍,其发病机制尚不清楚。既往研究提示微生物-肠道-脑(MGB)轴在卒中和抑郁中发挥作用。在本研究中,我们对PSD大鼠的微生物组成和功能以及肠道-脑代谢特征进行了表征。我们旨在探讨肠道微生物紊乱如何通过MGB轴参与PSD的发病机制。
采用16S rRNA基因序列和粪便代谢组分析来鉴定PSD大鼠的肠道微生物群及其功能代谢产物。然后,通过液相色谱质谱法对PSD大鼠前额叶皮质(PFC)中的脂质代谢特征进行分析。最后,探讨PSD发病过程中肠道与脑之间的潜在通路。
与对照组和卒中大鼠相比,PSD大鼠中有10个属(其中大多数属于厚壁菌门)显著改变,3种短链脂肪酸(SCFAs:丁酸、乙酸和戊酸)显著降低。同时,PSD大鼠肠道微生物的改变与这些SCFAs显著相关。与对照组和卒中大鼠相比,PSD大鼠PFC中的57种脂质代谢产物显著改变。此外,PSD大鼠中改变的SCFAs也与PFC中大多数紊乱的脂质代谢产物显著相关。
我们的研究结果表明,SCFAs可能是肠道与脑沟通的桥梁。厚壁菌门-SCFAs-脂质代谢可能是进一步研究MGB轴和PSD发病机制的潜在途径。