Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with <i>Bifidobacterium dentium</i>

Background: Accumulating evidence indicates that the gut microbiota can synthesize neurotransmitters as well as impact host-derived neurotransmitter levels. In the past, it has been challenging to decipher which microbes influence neurotransmitters due to the complexity of the gut microbiota. Method...

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Main Authors: Berkley Luck, Thomas D. Horvath, Kristen A. Engevik, Wenly Ruan, Sigmund J. Haidacher, Kathleen M. Hoch, Numan Oezguen, Jennifer K. Spinler, Anthony M. Haag, James Versalovic, Melinda A. Engevik
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/11/8/1091
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author Berkley Luck
Thomas D. Horvath
Kristen A. Engevik
Wenly Ruan
Sigmund J. Haidacher
Kathleen M. Hoch
Numan Oezguen
Jennifer K. Spinler
Anthony M. Haag
James Versalovic
Melinda A. Engevik
author_facet Berkley Luck
Thomas D. Horvath
Kristen A. Engevik
Wenly Ruan
Sigmund J. Haidacher
Kathleen M. Hoch
Numan Oezguen
Jennifer K. Spinler
Anthony M. Haag
James Versalovic
Melinda A. Engevik
author_sort Berkley Luck
collection DOAJ
description Background: Accumulating evidence indicates that the gut microbiota can synthesize neurotransmitters as well as impact host-derived neurotransmitter levels. In the past, it has been challenging to decipher which microbes influence neurotransmitters due to the complexity of the gut microbiota. Methods: To address whether a single microbe, <i>Bifidobacterium dentium,</i> could regulate important neurotransmitters, we examined <i>Bifidobacteria</i> genomes and explored neurotransmitter pathways in secreted cell-free supernatant using LC-MS/MS. To determine if <i>B. dentium</i> could impact neurotransmitters in vivo, we mono-associated germ-free mice with <i>B. dentium</i> ATCC 27678 and examined fecal and brain neurotransmitter concentrations. Results: We found that <i>B. dentium</i> possessed the enzymatic machinery to generate γ-aminobutyric acid (GABA) from glutamate, glutamine, and succinate. Consistent with the genome analysis, we found that <i>B. dentium</i> secreted GABA in a fully defined microbial media and elevated fecal GABA in <i>B. dentium</i> mono-associated mice compared to germ-free controls. We also examined the tyrosine/dopamine pathway and found that <i>B. dentium</i> could synthesize tyrosine, but could not generate L-dopa, dopamine, norepinephrine, or epinephrine. In vivo, we found that <i>B. dentium</i> mono-associated mice had elevated levels of tyrosine in the feces and brain. Conclusions: These data indicate that <i>B. dentium</i> can contribute to in vivo neurotransmitter regulation.
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spelling doaj.art-9957884028b544c28ae894be0f90959b2023-11-22T06:54:41ZengMDPI AGBiomolecules2218-273X2021-07-01118109110.3390/biom11081091Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with <i>Bifidobacterium dentium</i>Berkley Luck0Thomas D. Horvath1Kristen A. Engevik2Wenly Ruan3Sigmund J. Haidacher4Kathleen M. Hoch5Numan Oezguen6Jennifer K. Spinler7Anthony M. Haag8James Versalovic9Melinda A. Engevik10Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USABackground: Accumulating evidence indicates that the gut microbiota can synthesize neurotransmitters as well as impact host-derived neurotransmitter levels. In the past, it has been challenging to decipher which microbes influence neurotransmitters due to the complexity of the gut microbiota. Methods: To address whether a single microbe, <i>Bifidobacterium dentium,</i> could regulate important neurotransmitters, we examined <i>Bifidobacteria</i> genomes and explored neurotransmitter pathways in secreted cell-free supernatant using LC-MS/MS. To determine if <i>B. dentium</i> could impact neurotransmitters in vivo, we mono-associated germ-free mice with <i>B. dentium</i> ATCC 27678 and examined fecal and brain neurotransmitter concentrations. Results: We found that <i>B. dentium</i> possessed the enzymatic machinery to generate γ-aminobutyric acid (GABA) from glutamate, glutamine, and succinate. Consistent with the genome analysis, we found that <i>B. dentium</i> secreted GABA in a fully defined microbial media and elevated fecal GABA in <i>B. dentium</i> mono-associated mice compared to germ-free controls. We also examined the tyrosine/dopamine pathway and found that <i>B. dentium</i> could synthesize tyrosine, but could not generate L-dopa, dopamine, norepinephrine, or epinephrine. In vivo, we found that <i>B. dentium</i> mono-associated mice had elevated levels of tyrosine in the feces and brain. Conclusions: These data indicate that <i>B. dentium</i> can contribute to in vivo neurotransmitter regulation.https://www.mdpi.com/2218-273X/11/8/1091gut–brain axisneurotransmittersLC-MS/MSgut microbiome<i>Bifidobacteria</i>GABA
spellingShingle Berkley Luck
Thomas D. Horvath
Kristen A. Engevik
Wenly Ruan
Sigmund J. Haidacher
Kathleen M. Hoch
Numan Oezguen
Jennifer K. Spinler
Anthony M. Haag
James Versalovic
Melinda A. Engevik
Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with <i>Bifidobacterium dentium</i>
Biomolecules
gut–brain axis
neurotransmitters
LC-MS/MS
gut microbiome
<i>Bifidobacteria</i>
GABA
title Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with <i>Bifidobacterium dentium</i>
title_full Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with <i>Bifidobacterium dentium</i>
title_fullStr Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with <i>Bifidobacterium dentium</i>
title_full_unstemmed Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with <i>Bifidobacterium dentium</i>
title_short Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with <i>Bifidobacterium dentium</i>
title_sort neurotransmitter profiles are altered in the gut and brain of mice mono associated with i bifidobacterium dentium i
topic gut–brain axis
neurotransmitters
LC-MS/MS
gut microbiome
<i>Bifidobacteria</i>
GABA
url https://www.mdpi.com/2218-273X/11/8/1091
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