The DOI matches its Crossref record; 246 of the 246 references it cites were found in a registry or an index.
Serotonin, tryptophan metabolism and the brain-gut-microbiome axis
Abstract
The brain-gut axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract. Serotonin functions as a key neurotransmitter at both terminals of this network. Accumulating evidence points to a critical role for the gut microbiome in regulating normal functioning of this axis. In particular, it is becoming clear that the microbial influence on tryptophan metabolism and the serotonergic system may be an important node in such regulation. There is also substantial overlap between behaviours influenced by the gut microbiota and those which rely on intact serotonergic neurotransmission. The developing serotonergic system may be vulnerable to differential microbial colonisation patterns prior to the emergence of a stable adult-like gut microbiota. At the other extreme of life, the decreased diversity and stability of the gut microbiota may dictate serotonin-related health problems in the elderly. The mechanisms underpinning this crosstalk require further elaboration but may be related to the ability of the gut microbiota to control host tryptophan metabolism along the kynurenine pathway, thereby simultaneously reducing the fraction available for serotonin synthesis and increasing the production of neuroactive metabolites. The enzymes of this pathway are immune and stress-responsive, both systems which buttress the brain-gut axis. In addition, there are neural processes in the gastrointestinal tract which can be influenced by local alterations in serotonin concentrations with subsequent relay of signals along the scaffolding of the brain-gut axis to influence CNS neurotransmission. Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related brain-gut axis disorders.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“the gut microbiota are understood to impact the host GI serotonergic system (Hata et al., 2017;O'Mahony et al., 2015).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as O'Mahony et al., 2015
In the citing paper
“Indeed, it has been estimated that approximately 90% of available tryptophan is funneled towards the production of kynurenine (O' Mahony et al., 2015;Ruddick et al., 2006).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as O' Mahony et al., 2015
In the citing paper
“Notably, several psychobiotic strains within the Lactobacillus and Bifidobacterium genera, including Bifidobacterium dentium, Lactobacillus plantarum, and Lactobacillus brevis, can produce these neuroactive compounds (Schousboe and Waagepetersen, 2007; Barrett et al., 2012; O'Mahony et al., 2015).”
From Psychobiotics in mental health: insights from human clinical trials via the gut-brain axis (2026) · cites this paper as O'Mahony et al., 2015
In the citing paper
“For example, certain species of Lactobacillus and Bifidobacterium produce γ-aminobutyric acid (GABA), Streptococcus spp. and Enterococcus spp. produce serotonin, and Lactobacillus spp. produce acetylcholine [234,235].”
From Lactic Acid Bacteria in Raw-Milk Cheeses: From Starter Cultures to Probiotic Functions (2022) · cites this paper as [235]
In the citing paper
“So far, the possibility that modifications of the gut microbiota could negatively influence serotonergic signaling has only been suggested in pre-clinical studies, as data from clinical trials are still very limited [110]”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [110]
In the citing paper
“and some of the microbes residing in the gut can produce serotonin (i.e., Lactococcus lactis subsp.cremoris, L. lactis subsp.Lactis, Lactobacillus plantarum, Streptococcus thermophilus, E. coli K-12, Morganella morganii, Klebsiella pneumonia) [110,112,113].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [110]
In the citing paper
“The gut microbiota was implicated in regulating the levels of serotonin”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [110]
In the citing paper
“Indeed, low levels of this neurotransmitter have been correlated with the development of depression, while high levels have been linked also to colitis [110,111].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [110]
In the citing paper
“Activation of stress-responsive TDO or immune-responsive IDO can limit the availability of tryptophan for serotonin synthesis and increase the downstream production of neurotoxic or neuroprotective metabolites (31).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [31]
In the citing paper
“Thus, it is likely that the reach of these neurotransmitters can go beyond the local effects and could have important implications for CNS functioning (378).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [378]
In the citing paper
“Tryptophan metabolism, specifically the main pathways leading to the production of 5-HT, kynurenine, and indole derivatives, appears to be closely regulated by the gut microbiota (378, 387).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [378]
In the citing paper
“Additionally, it has been reported that dietary flavonoids (polyphenols) are associated with gut microbiome regulation, and these microbiomes can prevent and treat depression by increasing the synthesis of serotonin, which is a neurotransmitter in the body [16,17,18].”
From Flavonoid-rich orange juice intake and altered gut microbiome in young adults with depressive symptom: a randomized controlled study (2020) · cites this paper as [17]
In the citing paper
“Additionally, it has been reported that dietary flavonoids (polyphenols) are associated with gut microbiome regulation, and these microbiomes can prevent and treat depression by increasing the synthesis of serotonin, which is a neurotransmitter in the body [16,17,18].”
From Flavonoid-rich orange juice intake and altered gut microbiome in young adults with depressive symptom: a randomized controlled study (2020) · cites this paper as [17]
In the citing paper
“In particular, metabolites of the spermidine and kynurenine pathways are associated with the gut microbiota as well as the physiology of the host231,232.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [231]
In the citing paper
“There is evidence to suggest that serotonin (5-hydroxytryptamine, 5-HT) may be a nexus for the gut-brain-microbiome axis [23].”
From Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders (2018) · cites this paper as [23]
Citations
Cites
Diet rapidly and reproducibly alters the human gut microbiome
David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., et al. (2014) · Nature · doi:10.1038/nature12820 · Cited by 10,100
A core gut microbiome in obese and lean twins
Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., et al. (2009) · Nature · doi:10.1038/nature07540 · Cited by 7,823
Human gut microbiome viewed across age and geography
Yatsunenko, T., Rey, F. E., Manary, M. J., Trehan, I., Dominguez-Bello, M. G., Contreras, M., Magris, M., Hidalgo, G., Baldassano, R. N., Anokhin, A. P., et al. (2012) · Nature · doi:10.1038/nature11053 · Cited by 7,815
Effects of stress throughout the lifespan on the brain, behaviour and cognition
Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2639 · Cited by 6,256
Diversity, stability and resilience of the human gut microbiota
Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K., & Knight, R. (2012) · Nature · doi:10.1038/nature11550 · Cited by 5,533
Dominguez-Bello, M. G., Costello, E. K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N., & Knight, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002601107 · Cited by 4,774
Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Cryan, J. F., & Dinan, T. G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3346 · Cited by 4,572
Self-citationBravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., Bienenstock, J., & Cryan, J. F. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102999108 · Cited by 3,888
Self-citationThe gut microbiota--masters of host development and physiology
Sommer, F., & Bäckhed, F. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro2974 · Cited by 3,681
Gut microbiota composition correlates with diet and health in the elderly
Claesson, M. J., Jeffery, I. B., Conde, S., Power, S. E., O’Connor, E. M., Cusack, S., Harris, H. M. B., Coakley, M., Lakshminarayanan, B., O’Sullivan, O., et al. (2012) · Nature · doi:10.1038/nature11319 · Cited by 3,314
Research works printed but not linked: 5
- Shishov, 2009, [Amine neuromediators, their precursors, and oxidation products in the culture of Escherichia coli K-12], Prikladnaia biokhimiia i mikrobiologiia, 45, 550
- Clarke, 2014, Priming for health: the gut microbiota acquired early in life regulates physiology, Brain Behav Acta Paediatrica, 10.1111/apa.12674 · DOI · Paper page
- Clarke, 2014, Gut microbiota: the neglected endocrine organ, Mol Endocrinol, me20141108
- Wall, 2009, Role of gut microbiota in early infant development, Clin Med Pediatr, 3, 45, 10.4137/CMPed.S2008 · DOI
- O’Mahony, 2010, Early-life dysbiosis-induced visceral hypersensitivity in adulthood, Gastroenterology, 138, S4
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
Self-citationIndigenous bacteria from the gut microbiota regulate host serotonin biosynthesis
Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., Nagler, C. R., Ismagilov, R. F., Mazmanian, S. K., & Hsiao, E. Y. (2015) · Cell · doi:10.1016/j.cell.2015.02.047 · Cited by 3,614
The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00025 · Cited by 3,043
“Microorganisms can influence CNS processes bidirectionally via the vagus nerve (12) and through modulation of the immune system (6), the hypothalamic-pituitary-adrenal (HPA) axis (13, 14), and tryptophan metabolism (15), along with their ability to synthetize a number of neurotransmitters (16–18) and produce metabolit…”
BackgroundSalminen, S., Collado, M. C., Endo, A., Hill, C., Lebeer, S., Quigley, E. M. M., Sanders, M. E., Shamir, R., Swann, J. R., Szajewska, H., et al. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00440-6 · Cited by 2,488
Swanson, K. S., Gibson, G. R., Hutkins, R., Reimer, R. A., Reid, G., Verbeke, K., Scott, K. P., Holscher, H. D., Azad, M. B., Delzenne, N. M., et al. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0344-2 · Cited by 2,196
Metadata
- Authors
- O’Mahony, S. M., Clarke, G., Borre, Y. E., Dinan, T. G., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- Corresponding author
- Clarke, G.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 277
- Pages
- 32-48
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W1972237932
- Cited by
- 2,012
- References
- 246
- Citations by year
- 2026: 185 · 2025: 225 · 2024: 246 · 2023: 211 · 2022: 214 · 2021: 222 · 2020: 199 · 2019: 163 · 2018: 122 · 2017: 104 · 2016: 73 · 2015: 41
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health Research Board (HRA_POR/2011/23, HRA_POR/2012/32)
- Science Foundation Ireland (02/CE/B124, 07/CE/B1368, SFI/12/RC/2273)
- Seventh Framework Programme (201 714, FP7/2007–2013)
- Brain and Behavior Research Foundation (20771)
- National Alliance for Research on Schizophrenia and Depression
- GlaxoSmithKline
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- serotonin, tryptophan metabolism, gut-brain axis, gut microbiota, kynurenine pathway, serotonergic system, neuroactive metabolites, gut-brain signaling, microbial colonization, gut microbiota diversity, neuroimmune interactions, stress response
- MeSH terms
- Animals, Behavior, Brain, Humans, Serotonin, Tryptophan, Gastrointestinal Tract, Microbiota
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
