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

Abstract

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.

Metabolomics and Self-Reported Depression, Anxiety, and Phobic Symptoms in the VA Normative Aging Study

“…These metabolites covered two pathways, and perturbations to these pathways have previously been observed in mental health outcomes [ 31 ]. Metabolomic studies have implicated alterations to leucine, tyrosine, and methionine pathways in mental health conditions such as anxiety and depression [ 32 ]. Likewise, our study found evidence that may suggest that higher levels of the leucine metabolite 3-hydroxy-2-ethylpropionate were associated with abnormal scores across all three BSI subscales of interest.…”

Recent Progress in Mass Spectrometry-Based Metabolomics in Major Depressive Disorder Research

“…This was partly explained by the different changes in tryptophan pathway metabolites and neurotransmitters along the gut-brain axis. The relationship between microbial metabolites in feces and neurotransmitters in the prefrontal cortex of depressed mice was also explored using targeted metabolomics [91]. This suggested that the disruption of microbial metabolites may affect prefrontal cortex neurotransmitter levels, leading to depressive episodes.…”

Engineered Escherichia coli Nissle 1917 for the prevention of uremic toxin accumulation in chronic kidney disease

“…Besides being generally utilized as a protein building block, L-tyrosine is an amino acid precursor of norepinephrine and dopamine. Both norepinephrine and dopamine have an important role in the pathogenesis of depression [107].…”