Associations Between Disordered Microbial Metabolites and Changes of Neurotransmitters in Depressed Mice

作者全名："Xie, Jing; Wang, Ying; Zhong, Qi; Bai, Shun-jie; Zhou, Chan-juan; Tian, Tian; Chen, Jian-jun"

作者地址："[Xie, Jing] Chongqing Univ Cent Hosp, Peoples Hosp Chongqing 4, Chongqing Emergency Med Ctr, Dept Endocrinol, Chongqing, Peoples R China; [Wang, Ying] Chongqing Med Univ, Dept Rehabil, Affiliated Hosp 2, Chongqing, Peoples R China; [Zhong, Qi; Chen, Jian-jun] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Bai, Shun-jie] Chongqing Med Univ, Dept Lab Med, Affiliated Hosp 1, Chongqing, Peoples R China; [Zhou, Chan-juan] Chongqing Med Univ, Cent Lab, Yongchuan Hosp, Chongqing, Peoples R China; [Tian, Tian] Guizhou Med Univ, Dept Neurol, Affiliated Hosp, Guizhou, Peoples R China"

通信作者："Chen, JJ (通讯作者)，Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China."

来源：FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:000806051600001

JCR分区：Q2

影响因子：5.7

年份：2022

卷号：12

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：depression; amino acids; microbial metabolites; neurotransmitters; prefrontal cortex

摘要："BackgroundsMany pieces of evidence demonstrated that there were close relationships between gut microbiota and depression. However, the specific molecular mechanisms were still unknown. Here, using targeted metabolomics, this study was conducted to explore the relationships between microbial metabolites in feces and neurotransmitters in prefrontal cortex of depressed mice. MethodsChronic unpredictable mild stress (CUMS) model of depression was built in this study. Targeted liquid chromatography-mass spectrometry analysis was used to detect the microbial metabolites in feces and neurotransmitters in prefrontal cortex of mice. Both univariate and multivariate statistical analyses were applied to identify the differential microbial metabolites and neurotransmitters and explore relationships between them. ResultsNinety-eight differential microbial metabolites (mainly belonged to amino acids, fatty acids, and bile acids) and 11 differential neurotransmitters (belonged to tryptophan pathway, GABAergic pathway, and catecholaminergic pathway) were identified. Five affected amino acid-related metabolic pathways were found in depressed mice. The 19 differential microbial metabolites and 10 differential neurotransmitters were found to be significantly correlated with depressive-like behaviors. The two differential neurotransmitters (tyrosine and glutamate) and differential microbial metabolites belonged to amino acids had greater contributions to the overall correlations between microbial metabolites and neurotransmitters. In addition, the significantly decreased L-tyrosine as microbial metabolites and tyrosine as neurotransmitter had the significantly positive correlation (r = 0.681, p = 0.0009). ConclusionsThese results indicated that CUMS-induced disturbances of microbial metabolites (especially amino acids) might affect the levels of neurotransmitters in prefrontal cortex and then caused the onset of depression. Our findings could broaden the understanding of how gut microbiota was involved in the onset of depression."

基金机构：Natural Science Foundation Project of China [81701360]; Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0084]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202100420]; Chongqing Yuzhong District Science and Technology Commission [20190115]

基金资助正文："Funding This work was supported by the Natural Science Foundation Project of China (81701360), the Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0084), the Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202100420), and the Chongqing Yuzhong District Science and Technology Commission (20190115)."