Abstract
It has been reported that monoamine neurotransmitters can be produced by gut microbiota, and that several related metabolites of amino acids in these pathways are associated with nervous system (NVS) diseases. Herein, we focused on three pathways, namely, phenylalanine (Phe), tryptophan (Trp), and glutamic acid (Glu), and established an underivatized liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the quantification of nineteen monoamine neurotransmitters and related metabolites in the gut microbiota. The neurotransmitters and related metabolites included Phe, tyrosine (Tyr), l-dopa (Dopa), dopamine (DA), 3-methoxytyramine, Trp, hydroxytryptophan, 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), kynurenine (KN), kynurenic acid (KYNA), melatonin, tryptamine (TA), indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), indolyl-3-propionic acid (IPA), Glu, gamma-aminobutyric acid (GABA), and acetylcholine (Ach). A fluoro-phenyl bonded column was used for separation, and the mobile phase consisted of methanol:acetonitrile (1:1) and water, with 0.2% formic acid in both phases. The compounds exhibited symmetric peak shapes and sufficient sensitivity under a total analysis time of 8.5 min. The method was fully validated with acceptable linearity, accuracy, precision, matrix effect, extraction recovery, and stability. The results showed that neurotransmitters, such as Dopa, DA, 5-HT, GABA, and Ach, were present in the gut microbiota. The metabolic pathway of Trp was disordered under depression, with lower levels of 5-HT, 5-HIAA, KN, KYNA, TA, ILA, IAA, IPA, and Glu, and a higher ratio of KYNA/KN. In addition, some first-line NVS drugs, such as sertraline, imipramine, and chlorpromazine, showed regulatory potential on these pathways in the gut microbiota.
Highlights
Nervous system (NVS) diseases are causing increasing problems globally [1]
Conclusions a novel, simple, and underivatized LC-MS/MS method for the quantification of nineteen monoamine neurotransmitters and metabolites related to the nervous system (NVS) was developed
The method was suitable for intestinal bacterial samples and focused on three pathways, namely, Phe, Trp, and glutamic acid (Glu)
Summary
Nervous system (NVS) diseases are causing increasing problems globally [1]. According to the reports of the World Health Organization, fast-paced work or increased pressure cause depression, anxiety, schizophrenia, etc.; while the neurodegenerative diseases caused by aging (such as Alzheimer’s disease and Parkinson’s disease) have influenced the quality of daily life to a considerable extent [2]. Several monoamine neurotransmitters, such as gamma-aminobutyric acid (GABA) [9], tryptamine (TA) [10], catecholamines, and serotonin (5-HT) [11], have been reported to be generated or metabolized by gut microbes. These absorbed molecules in vivo could regulate central and peripheral NVS functions via signaling pathways [12]. Gut microbes themselves, or their monoamine metabolites on amino acid catabolism pathways (kynurenine, etc.) can activate neural pathways or the immune system and affect the neuronal transcription in the host’s brain, leading to the changes in host behavior [13,14]. Though much remains to be explored, these metabolites on amino acid pathways have been uncovered as signals in the gut microbiota, and they play essential roles in the microbiota–host crosstalk [16]
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