Page 9 - JCBP-2-4

Journal of Clinical and
Basic Psychosomatics FND and gut microbiome

Table 1. Microbial production of neurotransmitters 21,46,47
Neurotransmitters Precursors Gut microbiota producers
Acetylcholine Choline Bacillus, Escherichia, Lactobacillus, and Staphylococcus
Dopamine Tyrosine, L-DOPA Bacillus, Escherichia, Serratia, and Staphylococcus
GABA Acetate Bacteroides, Bifidobacterium, Escherichia, Eubacterium,
Lactobacillus, Parabacteroides, and Pseudomonas
Glutamate Acetate Bacteroides, Brevibacterium, Campylobacter,
Corynebacterium, and Lactobacillus
Histamine Histidine Klebsiella
Noradrenaline or norepinephrine Tyrosine Bacillus, Escherichia, and Saccharomyces
Phenylethylamine Phenylalanine Staphylococcus
Serotonin 5-hydroxytryptophan, tryptophan Candida, Clostridium, Enterococcus, Escherichia,
Lactobacillus, Staphylococcus, and Streptococcus
Tryptamine Tryptophan Clostridium, Ruminococcus, and Staphylococcus
Tyramine Tyrosine Providencia and Staphylococcus

of the gut microbiome may disrupt neurotransmitter 4. Gut microbiome dysbiosis and
synthesis and lead to mental disorders. 46,47 neuroinflammation
Short-chain fatty acids (SCFAs), including acetate, The gut microbiome can modulate host immune activity by
butyrate, and propionate, are metabolic lipids produced regulating the production of pro-inflammatory cytokines,
by gut microbes through the fermentation of dietary fiber. which afterward influence the HPA axis to release
The major gut bacterial producers of SCFAs are listed in corticotrophin-releasing hormone, adrenocorticotropic
Table 2. 48-50 SCFAs have the ability to influence the host hormone, and cortisol. The HPA axis is modulated
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energy balance, hormones, and metabolism, regulating by diverse stressors such as microbial infection and
the epigenetics, immune system, and neuroplasticity psychological stress; the toll-like receptors (TLRs) recognize
within the CNS, and they also constitute an important gut- pathogenic microorganisms or adverse conditions leading
brain signaling pathway through the vagus nerve. Other to an activation of the nuclear factor kappa B pathway,
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microbial metabolites, such as alpha-tocopherol, indole, cytokine production, and ultimately HPA response.
59
p-aminobenzoate, secondary bile acids, and tyramine, Besides, the HPA response mediated by stress can also be
affect the production and secretion of serotonin by the regulated by serotonin neurotransmission. 60
enteroendocrine cells. The mechanism underlying the
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production of gut hormones acts through the activation of Regarding neuroinflammation, several clinical studies
G protein-coupled receptors by the SCFAs within the colon, have demonstrated reduced diversity and dysbiosis of the
which enhance the liberation of peptide YY and glucagon- gut microbiome. Nevertheless, it is still unclear whether
like peptide 1 from enteroendocrine L-cells. 53,54 These it is dysbiosis that actively modulates inflammatory
hormones in turn can affect mood, memory, and learning processes within the CNS, or whether it is only due
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processes, increasing neuroplasticity and neuroprotection to an effect of neuroinflammation itself. It has been
in the hippocampus, and reducing beta-amyloid plaques demonstrated that dysbiosis increases the permeability of
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and microglial activation. In addition, ghrelin, leptin, and the gut epithelial barrier, exposing the host to greater levels
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insulin are other metabolic hormones influenced by SCFAs of microbial metabolites and to an increased quantity
that affect brain function. 45 of cell wall components, such as bacterial extracellular
vesicles (BEVs), lipoteichoic acids (LTA), LPS, and various
Microbial enzymatic processes can produce the
neurotoxins D-lactic acid and ammonium compounds, peptidoglycan (PG), which could exert a significant impact
on the pathogenesis of neurological diseases.
and other neuroactive metabolites, such as amino acids
(tryptophan and tyramine), lipopolysaccharide (LPS), LPS and LTA can interact with several TLRs expressed
long-chain fatty acids, trimethylamine-N-oxide, and by human neurons, and this ligand-receptor interaction
polysaccharide A, which induce peripheral immune cell triggers the production of inflammatory substances, such
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migration into the brain and cause neuroinflammation, as ROS, which can mediate microglial activation. In
44
although it is complicated to directly assess to what extent addition, neuronal death by caspase-3-dependent apoptosis
microbial metabolism affects CNS activity. 57 is promoted by pro-inflammatory cytokines liberated in

Volume 2 Issue 4 (2024) 3 doi: 10.36922/jcbp.4160