Tryptophan metabolism and gut-brain homeostasis
Open accessAbstract
Tryptophan is an essential amino acid critical for protein synthesis in humans that has emerged as a key player in the microbiota-gut-brain axis. It is the only precursor for the neurotransmitter serotonin, which is vital for the processing of emotional regulation, hunger, sleep, and pain, as well as colonic motility and secretory activity in the gut. Tryptophan catabolites from the kynurenine degradation pathway also modulate neural activity and are active in the systemic inflammatory cascade. Additionally, tryptophan and its metabolites support the development of the central and enteric nervous systems. Accordingly, dysregulation of tryptophan metabolites plays a central role in the pathogenesis of many neurologic and psychiatric disorders. Gut microbes influence tryptophan metabolism directly and indirectly, with corresponding changes in behavior and cognition. The gut microbiome has thus garnered much attention as a therapeutic target for both neurologic and psychiatric disorders where tryptophan and its metabolites play a prominent role. In this review, we will touch upon some of these features and their involvement in health and disease.
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These bacteria are associated with the development of neuropsychiatric disorders, including autism spectrum disorders.
“these bacteria have been associated with the development of neuropsychiatric disorders, including autism spectrum disorders (205).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [205]
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Gu, Y., Jiang, L., Shui, M., Luo, H., Zhou, X., Zhang, S., Jiang, C., Huang, J., Chen, H., Tang, J., et al. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1452392 · Cited by 23 · see citing works
Harnessing Gut Microbiota for Biomimetic Innovations in Health and Biotechnology
Beltrán-Velasco, A. I., & Clemente‐Suárez, V. J. (2025) · Biomimetics · doi:10.3390/biomimetics10020073 · Cited by 23 · see citing works
Gut Microbiome and Metabolome Changes in Mice With Acute Vestibular Deficit
Li, F., Feng, Y., Liu, H., Kong, D., Hsueh, C., Shi, X., Wu, Q., Li, W., Wang, J., Zhang, Y., et al. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.821780 · Cited by 23 · see citing works
Traumatic Brain Injury and Gut Brain Axis: The Disruption of an Alliance
Ferrara, M., Bertozzi, G., Zanza, C., Longhitano, Y., Piccolella, F., Lauritano, E. C., Volonnino, G., Manetti, A. C., Maiese, A., & Russa, R. L. (2022) · Reviews on Recent Clinical Trials · doi:10.2174/1574887117666220622143423 · Cited by 23 · see citing works
Xanthurenic acid: A role in brain intercellular signaling
Maître, M., Taleb, O., Jeltsch‐David, H., Klein, C., & Mensah‐Nyagan, A. G. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16099 · Cited by 22 · see citing works
- Authors
- Roth, W., Zadeh, K., Vekariya, R., Ge, Y., & Mohamadzadeh, M.
- Affiliations
- University of Florida (US)
- Corresponding author
- Roth, William
- Mohamadzadeh, Mansour
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2021-03-15
- Volume
- 22
- Issue
- 6
- Pages
- 2973
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC8000752
- OpenAlex
- W3137164735
- Cited by
- 519
- References
- 194
- Citations by year
- 2026: 102 · 2025: 150 · 2024: 139 · 2023: 72 · 2022: 46 · 2021: 10
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (DK109560C, R01AI154630-01)
- 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, gut microbiota, serotonin, kynurenine pathway, tryptophan catabolites, neuroinflammation, enteric nervous system, neurological disorders, mental illness, microbiota-targeted therapy
- MeSH terms
- Gastrointestinal Microbiome, Brain, Colon, Homeostasis, Humans, Hunger, Kynurenine, Pain, Serotonin, Sleep, Tryptophan, Enteric Nervous System
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