Neurotransmitter modulation by the gut microbiota
Open accessAbstract
The gut microbiota - the trillions of bacteria that reside within the gastrointestinal tract - has been found to not only be an essential component immune and metabolic health, but also seems to influence development and diseases of the enteric and central nervous system, including motility disorders, behavioral disorders, neurodegenerative disease, cerebrovascular accidents, and neuroimmune-mediated disorders. By leveraging animal models, several different pathways of communication have been identified along the "gut-brain-axis" including those driven by the immune system, the vagus nerve, or by modulation of neuroactive compounds by the microbiota. Of the latter, bacteria have been shown to produce and/or consume a wide range of mammalian neurotransmitters, including dopamine, norepinephrine, serotonin, or gamma-aminobutyric acid (GABA). Accumulating evidence in animals suggests that manipulation of these neurotransmitters by bacteria may have an impact in host physiology, and preliminary human studies are showing that microbiota-based interventions can also alter neurotransmitter levels. Nonetheless, substantially more work is required to determine whether microbiota-mediated manipulation of human neurotransmission has any physiological implications, and if so, how it may be leveraged therapeutically. In this review this exciting route of communication along the gut-brain-axis, and accompanying data, are discussed.
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The intestinal microbiota and its metabolites can produce serotonin, norepinephrine, and GABA through stimulation of intestinal chromogranin cells, and these neurotransmitters can reach the brain and directly affect central nervous system function through the intestinal epithelium or the blood-brain barrier.
“The intestinal microbiota and its metabolites (e.g., SCFAs) can also produce serotonin, norepinephrine, and GABA through stimulation of intestinal chromogranin cells (52), and these neurotransmitters can reach the brain and directly affect central nervous system function through the intestinal epithelium or the BBB (24).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [52]
The capacity of gut bacteria to produce neurotransmitters, including γ-amino butyric acid, norepinephrine and dopamine, and to modulate host production of serotonin, seems relevant for the association between microbiota composition and gait speed.
“Namely, the capacity of gut bacteria to produce neurotransmitters, including γ-amino butyric acid, norepinephrine and dopamine, and to modulate the host production of serotonin, seems relevant for the association between microbiota composition and gait speed [102].”
From Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia (2019) · cites this paper as [102]
Preliminary human studies demonstrate that microbiota-based interventions can alter neurotransmitter concentrations.
“preliminary human studies demonstrate that microbiota-based interventions can alter neurotransmitter concentrations (28).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [28]
Animal studies provide evidence that microbial modulation of neurotransmitters may impact host physiology.
“Animal studies provide evidence that microbial modulation of these neurotransmitters may impact host physiology”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [28]
Several bacterial taxa affect tryptophan levels by direct utilization for growth or via tryptophanase expression.
“Several bacterial taxa can also affect tryptophan levels by direct utilization for growth or via tryptophanase expression (28, 203, 204)”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [28]
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- Authors
- Strandwitz, P.
- Affiliations
- Northeastern University (US)
- Corresponding author
- Strandwitz, Philip
- ORCID
- Strandwitz, Philip
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 1693
- Issue
- Pt B
- Pages
- 128-133
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC6005194
- OpenAlex
- W2807772034
- Cited by
- 1,527
- References
- 71
- Citations by year
- 2026: 182 · 2025: 264 · 2024: 250 · 2023: 252 · 2022: 213 · 2021: 191 · 2020: 120 · 2019: 47 · 2018: 8
- FWCI
- 8.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Brain Research (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Human Genome Research Institute (R01HG005824)
- National Institute of Allergy and Infectious Diseases (R01AI122286)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota, neurotransmitters, gut-brain axis, dopamine, norepinephrine, serotonin, GABA, neuroactive compounds, vagus nerve, neuroimmune interactions, neurodegenerative diseases, behavioral disorders, microbiota-targeted interventions
- MeSH terms
- Gastrointestinal Microbiome, Animals, Brain, Humans, Neurotransmitter Agents
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