Abstract
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, Bifidobacterium dentium, could regulate important neurotransmitters, we examined Bifidobacteria genomes and explored neurotransmitter pathways in secreted cell-free supernatant using LC-MS/MS. To determine if B. dentium could impact neurotransmitters in vivo, we mono-associated germ-free mice with B. dentium ATCC 27678 and examined fecal and brain neurotransmitter concentrations. Results: We found that B. dentium possessed the enzymatic machinery to generate γ-aminobutyric acid (GABA) from glutamate, glutamine, and succinate. Consistent with the genome analysis, we found that B. dentium secreted GABA in a fully defined microbial media and elevated fecal GABA in B. dentium mono-associated mice compared to germ-free controls. We also examined the tyrosine/dopamine pathway and found that B. dentium could synthesize tyrosine, but could not generate L-dopa, dopamine, norepinephrine, or epinephrine. In vivo, we found that B. dentium mono-associated mice had elevated levels of tyrosine in the feces and brain. Conclusions: These data indicate that B. dentium can contribute to in vivo neurotransmitter regulation.
Highlights
We first focused on the neurotransmitter generate γ-aminobutyric acid (GABA), which serves as the major inhibitory neurotransmitter of the enteric nervous system (ENS) and central nervous system (CNS) [59]
We found that B. dentium (6 genomes) and 10 other Bifidobacteria species contained all genes required to convert glutamine, glutamate, and succinate into
B. dentium had the molecular machinery to produce tyrosine, we found that B. dentium did not generate tyrosine in ZMB1 using LC-MS/MS analysis
Summary
One way gut microbes can interact with the ENS, and CNS is through the modulation of host neurotransmitters and/or related pathways. Consistent with this notion, select microbes have been found to produce a range of major neuroactive compounds including tyrosine, tryptophan, dopamine, norepinephrine, and Biomolecules 2021, 11, 1091. Methods: To address whether a single microbe, Bifidobacterium dentium, could regulate important neurotransmitters, we examined Bifidobacteria genomes and explored neurotransmitter pathways in secreted cell-free supernatant using LC-MS/MS. To determine if B. dentium could impact neurotransmitters in vivo, we mono-associated germ-free mice with B. dentium ATCC 27678 and examined fecal and brain neurotransmitter concentrations. We examined the tyrosine/dopamine pathway and found that
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