Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways

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 g...

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Main Authors: Shu-Rong Ma, Jin-Bo Yu, Jie Fu, Li-Bin Pan, Hang Yu, Pei Han, Zheng-Wei Zhang, Ran Peng, Hui Xu, Yan Wang
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/5/1377
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author Shu-Rong Ma
Jin-Bo Yu
Jie Fu
Li-Bin Pan
Hang Yu
Pei Han
Zheng-Wei Zhang
Ran Peng
Hui Xu
Yan Wang
author_facet Shu-Rong Ma
Jin-Bo Yu
Jie Fu
Li-Bin Pan
Hang Yu
Pei Han
Zheng-Wei Zhang
Ran Peng
Hui Xu
Yan Wang
author_sort Shu-Rong Ma
collection DOAJ
description 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), <span style="font-variant: small-caps;">l</span>-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.
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spelling doaj.art-6d827b47144f4f9fa0bc1121ac4a02582023-12-03T12:30:43ZengMDPI AGMolecules1420-30492021-03-01265137710.3390/molecules26051377Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic PathwaysShu-Rong Ma0Jin-Bo Yu1Jie Fu2Li-Bin Pan3Hang Yu4Pei Han5Zheng-Wei Zhang6Ran Peng7Hui Xu8Yan Wang9State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, ChinaIt 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), <span style="font-variant: small-caps;">l</span>-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.https://www.mdpi.com/1420-3049/26/5/1377monoamine neurotransmittersliquid chromatography–tandem mass spectrometry (LC-MS/MS)nervous system (NVS)gut microbiotatryptophanphenylalanine
spellingShingle Shu-Rong Ma
Jin-Bo Yu
Jie Fu
Li-Bin Pan
Hang Yu
Pei Han
Zheng-Wei Zhang
Ran Peng
Hui Xu
Yan Wang
Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways
Molecules
monoamine neurotransmitters
liquid chromatography–tandem mass spectrometry (LC-MS/MS)
nervous system (NVS)
gut microbiota
tryptophan
phenylalanine
title Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways
title_full Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways
title_fullStr Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways
title_full_unstemmed Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways
title_short Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways
title_sort determination and application of nineteen monoamines in the gut microbiota targeting phenylalanine tryptophan and glutamic acid metabolic pathways
topic monoamine neurotransmitters
liquid chromatography–tandem mass spectrometry (LC-MS/MS)
nervous system (NVS)
gut microbiota
tryptophan
phenylalanine
url https://www.mdpi.com/1420-3049/26/5/1377
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