抑郁症菌群可以改变肝脏代谢


Title:
Metabolite identification in fecal microbiota transplantation mouse livers and combined proteomics with chronic unpredictive mild stress mouse livers

DOI:
10.1038/s41398-017-0078-2


Abstract:
Major depressive disorder (MDD) is a common mood disorder. Gut microbiota may be involved in the pathogenesis of depression via the microbe-gut-brain axis. Liver is vulnerable to exposure of bacterial products translocated from the gut via the portal vein and may be involved in the axis. In this study, germ-free mice underwent fecal microbiota transplantation from MDD patients and healthy controls. Behavioral tests verified the depression model. Metabolomics using gas chromatography-mass spectrometry, nuclear magnetic resonance, and liquid chromatography-mass spectrometry determined the influence of microbes on liver metabolism. With multivariate statistical analysis, 191 metabolites were distinguishable in MDD mice from control (CON) mice. Compared with CON mice, MDD mice showed lower levels for 106 metabolites and higher levels for 85 metabolites. These metabolites are associated with lipid and energy metabolism and oxidative stress. Combined analyses of significantly changed proteins in livers from another depression model induced by chronic unpredictive mild stress returned a high score for the Lipid Metabolism, Free Radical Scavenging, and Molecule Transports network, and canonical pathways were involved in energy metabolism and tryptophan degradation. The two mouse models of depression suggest that changes in liver metabolism might be involved in the pathogenesis of MDD. Conjoint analyses of fecal, serum, liver, and hippocampal metabolites from fecal microbiota transplantation mice suggested that aminoacyl-tRNA biosynthesis significantly changed and fecal metabolites showed a close relationship with the liver. These findings may help determine the biological mechanisms of depression and provide evidence about "depression microbes" impacting on liver metabolism.

All Authors:
Bo Li,Kenan Guo,Li Zeng,Benhua Zeng,Ran Huo,Yuanyuan Luo,Haiyang Wang,Meixue Dong,Peng Zheng,Chanjuan Zhou,Jianjun Chen,Yiyun Liu,Zhao Liu,Liang Fang,Hong Wei,Peng Xie

First Authors:
Bo Li

Correspondence:
Hong Wei,Peng Xie


摘要:

       将重度抑郁症(MDD)患者或健康个体的粪菌移植给小鼠,行为测验表明MDD小鼠可作为抑郁症模型; 采用多种方法分析菌群对肝脏代谢组的影响,发现MDD小鼠体内有191种代谢物水平发生变化,其中106种降低,85种升高,这些代谢物水平的变化与脂质和能量代谢、氧化应激有关;结合另一种抑郁症小鼠的蛋白质组分析,表明MDD发病机理可能涉及肝脏代谢改变;对MDD小鼠多部位样本的代谢物进行综合分析,发现氨酰tRNA生物合成在MDD小鼠中显著改变,证实粪便中的代谢物与肝脏的最相关。


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