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Article

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

by
Shu-Rong Ma
,
Jin-Bo Yu
,
Jie Fu
,
Li-Bin Pan
,
Hang Yu
,
Pei Han
,
Zheng-Wei Zhang
,
Ran Peng
,
Hui Xu
and
Yan Wang
*
State 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, China
*
Author to whom correspondence should be addressed.
Molecules 2021, 26(5), 1377; https://doi.org/10.3390/molecules26051377
Submission received: 28 January 2021 / Revised: 22 February 2021 / Accepted: 2 March 2021 / Published: 4 March 2021
(This article belongs to the Section Analytical Chemistry)
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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.
Keywords: monoamine neurotransmitters; liquid chromatography–tandem mass spectrometry (LC-MS/MS); nervous system (NVS); gut microbiota; tryptophan; phenylalanine; glutamic acid monoamine neurotransmitters; liquid chromatography–tandem mass spectrometry (LC-MS/MS); nervous system (NVS); gut microbiota; tryptophan; phenylalanine; glutamic acid

Share and Cite

MDPI and ACS Style

Ma, S.-R.; Yu, J.-B.; Fu, J.; Pan, L.-B.; Yu, H.; Han, P.; Zhang, Z.-W.; Peng, R.; Xu, H.; Wang, Y. Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways. Molecules 2021, 26, 1377. https://doi.org/10.3390/molecules26051377

AMA Style

Ma S-R, Yu J-B, Fu J, Pan L-B, Yu H, Han P, Zhang Z-W, Peng R, Xu H, Wang Y. Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways. Molecules. 2021; 26(5):1377. https://doi.org/10.3390/molecules26051377

Chicago/Turabian Style

Ma, Shu-Rong, Jin-Bo Yu, Jie Fu, Li-Bin Pan, Hang Yu, Pei Han, Zheng-Wei Zhang, Ran Peng, Hui Xu, and Yan Wang. 2021. "Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways" Molecules 26, no. 5: 1377. https://doi.org/10.3390/molecules26051377

APA Style

Ma, S.-R., Yu, J.-B., Fu, J., Pan, L.-B., Yu, H., Han, P., Zhang, Z.-W., Peng, R., Xu, H., & Wang, Y. (2021). Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways. Molecules, 26(5), 1377. https://doi.org/10.3390/molecules26051377

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