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.
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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]
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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
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