Focus on the essentials: tryptophan metabolism and the microbiome-gut-brain axis
Open accessAbstract
The gut-brain axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract, in which serotonin (5-HT) functions as a key neurotransmitter. Recent research has increasingly concentrated on tryptophan, the precursor to 5-HT and on the microbial regulation of tryptophan metabolism, with an emphasis on host-microbe control over kynurenine pathway metabolism and microbial-specific pathways that generate bioactive tryptophan metabolites. Here, we critically assess recent progress made towards a mechanistic understanding of the microbial regulation of tryptophan metabolism and microbiota-gut-brain axis homeostasis highlighting the role tryptophan metabolism plays in preclinical and clinical neuroscience and in the challenge to improve our understanding of how perturbed tryptophan metabolism contributes to stress-related psychiatric disorders.
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Preclinical studies have demonstrated that some indole metabolites may exert negative effects on brain health, such as causing depression-like behavior.
“preclinical studies have demonstrated that some indole metabolites may also exert negative effects on brain health, such as causing depression-like behavior [33].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [33]
High levels of 5-HT may be caused by gastrointestinal 5-HT hypersecretion produced by enterochromaffin cells in the gut, involved in motility and secretion.
“High levels of 5′HT may be caused by a gastrointestinal 5′HT hypersecretion, produced by the enterochromaffin cells in the gut and it is involved in functions such as motility and secretion [189].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [189]
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Self-citation
- Authors
- Gheorghe, C. E., Martin, J. A., Manriquez, F. V., Dinan, T. G., Cryan, J. F., & Clarke, G.
- Affiliations
- University College Cork (IE)
- Corresponding author
- Clarke, Gerard
- Venue
- Current Opinion in Pharmacology
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 48
- Pages
- 137-145
- ISSN
- 1471-4892 (ISSN-L)
- OpenAlex
- W2980487229
- Cited by
- 212
- References
- 65
- Citations by year
- 2026: 25 · 2025: 36 · 2024: 38 · 2023: 27 · 2022: 41 · 2021: 28 · 2020: 16 · 2019: 1
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Opinion in Pharmacology (acceptedVersion)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (acceptedVersion)
- Cork Open Research Archive (University College Cork, Ireland) (submittedVersion, cc-by-nc-nd)
- Funders
- Science Foundation Ireland (12/RC/2273)
- Association for Progressive Communications
- Air Force Office of Scientific Research (FA9550-17-1-006)
- Servier
- AstraZeneca
- H. Lundbeck A/S
- Janssen Biotech
- Mead Johnson Nutrition
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- tryptophan metabolism, gut-brain axis, microbiome, serotonin, kynurenine pathway, microbial metabolites, host-microbe interactions, stress-related psychiatric disorders
- MeSH terms
- Gastrointestinal Microbiome, Animals, Mental Disorders, Brain, Humans, Indoles, Kynurenine, Tryptophan
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