Serotonin, tryptophan metabolism and the brain-gut-microbiome axis

O’Mahony, S.M.; Clarke, G.; Borre, Y.E.; Dinan, T.G.; Cryan, J.F.

doi:10.1016/j.bbr.2014.07.027

Cited by 2,012Gut microbiota and healthTryptophan and brain disordersGastrointestinal motility and disorders

Serotonin, tryptophan metabolism and the brain-gut-microbiome axis

O’Mahony, S.M., Clarke, G., Borre, Y.E., Dinan, T.G., Cryan, J.F.·2015·Behavioural Brain Research

DOI 10.1016/j.bbr.2014.07.027

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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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The gut microbiota impact the host GI serotonergic system.
“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
Several psychobiotic strains within Lactobacillus and Bifidobacterium genera, including Bifidobacterium dentium, Lactobacillus plantarum, and Lactobacillus brevis, can produce neuroactive compounds such as GABA and serotonin.
“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
Certain species of Lactobacillus and Bifidobacterium produce GABA, Streptococcus spp. and Enterococcus spp. produce serotonin, and Lactobacillus spp. produce acetylcholine.
“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]
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.
“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]
Some microbes residing in the gut can produce serotonin.
“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]

The gut microbiota is implicated in regulating the levels of serotonin.
“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]
Low levels of serotonin have been correlated with the development of depression, while high levels have been linked to colitis.
“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]
Activation of stress-responsive TDO or immune-responsive IDO limits tryptophan availability for serotonin synthesis and increases production of neurotoxic or neuroprotective metabolites.
“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]
It is likely that the reach of microbially derived neurotransmitters can go beyond local effects and could have important implications for CNS functioning.
“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]
Tryptophan metabolism, specifically the main pathways leading to production of 5-HT, kynurenine, and indole derivatives, appears to be closely regulated by the gut microbiota.
“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]
Gut microbiomes can prevent and treat depression by increasing serotonin synthesis.
“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]
Dietary flavonoids (polyphenols) are associated with gut microbiome regulation.
“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]
Metabolites of the spermidine and kynurenine pathways are associated with the gut microbiota as well as the physiology of the host.
“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]
Serotonin may be a nexus for the gut-brain-microbiome axis.
“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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Acute Tryptophan Depletion. Part I: Rationale and Methodology
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A physiological view of the central and peripheral mechanisms that regulate the release of catecholamines at the adrenal medulla
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Time course of expression of neuropeptide Y, calcitonin gene‐related peptide, and NADPH diaphorase activity in neurons of the developing murine bowel and the appearance of 5‐hydroxytryptamine in mucosal enterochromaffin cells
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Alterations in Expression of p11 and SERT in Mucosal Biopsy Specimens of Patients With Irritable Bowel Syndrome
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Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome
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5-HT in the enteric nervous system: gut function and neuropharmacology
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Tryptophan catabolism in females with irritable bowel syndrome: relationship to interferon‐gamma, severity of symptoms and psychiatric co‐morbidity
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Cellular changes in the enteric nervous system during ageing
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A Distinct Profile of Tryptophan Metabolism along the Kynurenine Pathway Downstream of Toll-Like Receptor Activation in Irritable Bowel Syndrome
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Immune dysregulation in autism spectrum disorder
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Exercise, Serum Free Tryptophan, and Central Fatigue
Fernstrom, J. D., & Fernstrom, M. H. (2006) · The Journal of Nutrition · doi:10.1093/jn/136.2.553s · Cited by 117 · see citing works
Altered cognitive function of prefrontal cortex during error feedback in patients with irritable bowel syndrome, based on FMRI and dynamic causal modeling
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Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense.
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Ageing and the gut
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Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects
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Role of Gut Microbiota in Early Infant Development
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Kynurenic Acid in the Digestive System–-New Facts, New Challenges
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Cognitive performance in irritable bowel syndrome: evidence of a stress-related impairment in visuospatial memory
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Acute Tryptophan Depletion. Part II: Clinical Effects and Implications
Bell, C., Hood, S. D., & Nutt, D. (2005) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/j.1440-1614.2005.01628.x · Cited by 101 · see citing works
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Development of raphe serotonin neurons from specification to guidance
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Age-related decline of serotonin transporters in living human brain of healthy males
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Increased populations of endocrine cells in Crohn's ileitis
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The Function of Lactic Acid Bacteria on Biogenic Amines Production by Food-Borne Pathogens in Arginine Decarboxylase Broth
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Epigenetic Risk Factors in PTSD and Depression
Raabe, F. J., & Spengler, D. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00080 · Cited by 94 · see citing works
Tryptophan synthase: a mine for enzymologists
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Programming of sympathoadrenal function
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Cognitive-Behavioral Group Therapy for Patients with Irritable Bowel Syndrome
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Stress and visceral pain: Focusing on irritable bowel syndrome
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Pharmacologic and Complementary and Alternative Medicine Therapies for Irritable Bowel Syndrome
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Immune Dysregulation in Autism Spectrum Disorder
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5-HT2B receptors modulate visceral hypersensitivity in a stress-sensitive animal model of brain-gut axis dysfunction
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Consequences of Citrobacter rodentium infection on enteroendocrine cells and the enteric nervous system in the mouse colon
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Serotonin Promotes the Differentiation of Glutamate Neurons in Organotypic Slice Cultures of the Developing Cerebral Cortex
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The Microbiota-Gut-Brain Axis
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 · see citing works
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Indigenous 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 · see citing works
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 · see citing works
“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…”
Background
The International Scientific Association of Probiotics and Prebiotics (ISAPP) Consensus Statement on the Definition and Scope of Postbiotics
Salminen, 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 · see citing works
The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics
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 · see citing works
The neuroactive potential of the human gut microbiota in quality of life and depression
Valles-Colomer, M., Falony, G., Darzi, Y., Tigchelaar, E. F., Wang, J., Tito, R. Y., Schiweck, C., Kurilshikov, A., Joossens, M., Wijmenga, C., et al. (2019) · Nature Microbiology · doi:10.1038/s41564-018-0337-x · Cited by 1,963 · see citing works
Large-scale association analyses identify host factors influencing human gut microbiome composition
Kurilshikov, A., Medina-Gomez, C., Bacigalupe, R., Radjabzadeh, D., Wang, J., Demirkan, A., Le Roy, C. I., Raygoza Garay, J. A., Finnicum, C. T., Liu, X., et al. (2021) · Nature Genetics · doi:10.1038/s41588-020-00763-1 · Cited by 1,786 · see citing works
Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat
Kelly, J. R., Borre, Y., O' Brien, C., Patterson, E., El Aidy, S., Deane, J., Kennedy, P. J., Beers, S., Scott, K., Moloney, G., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.07.019 · Cited by 1,683 · see citing works
Self-citation
The central nervous system and the gut microbiome
Sharon, G., Sampson, T. R., Geschwind, D. H., & Mazmanian, S. K. (2016) · Cell · doi:10.1016/j.cell.2016.10.027 · Cited by 1,513 · see citing works
Human gut microbiome: Hopes, threats and promises
Cani, P. D. (2018) · Gut · doi:10.1136/gutjnl-2018-316723 · Cited by 1,386 · see citing works
Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders
Kelly, J. R., Kennedy, P. J., Cryan, J. F., Dinan, T. G., Clarke, G., & Hyland, N. P. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00392 · Cited by 1,110 · see citing works
Self-citation
Control of brain development, function, and behavior by the microbiome
Sampson, T. R., & Mazmanian, S. K. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.011 · Cited by 1,093 · see citing works
Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain
Gao, K., Mu, C.-L., Farzi, A., & Zhu, W.-Y. (2020) · Advances in Nutrition · doi:10.1093/advances/nmz127 · Cited by 1,029 · see citing works
The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates
Franceschi, C., Garagnani, P., Morsiani, C., Conte, M., Santoro, A., Grignolio, A., Monti, D., Capri, M., & Salvioli, S. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00061 · Cited by 945 · see citing works
From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways
Rogers, G. B., Keating, D. J., Young, R. L., Wong, M.-L., Licinio, J., & Wesselingh, S. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.50 · Cited by 969 · see citing works
Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis
Jenkins, T., Nguyen, J., Polglaze, K., & Bertrand, P. (2016) · Nutrients · doi:10.3390/nu8010056 · Cited by 904 · see citing works
Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration
Dinan, T. G., & Cryan, J. F. (2017) · The Journal of Physiology · doi:10.1113/jp273106 · Cited by 813 · see citing works
Self-citation
Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: gut microbiota, glial reaction and TLR4/TNF-α signaling pathway
Sun, M.-F., Zhu, Y.-L., Zhou, Z.-L., Jia, X.-B., Xu, Y.-D., Yang, Q., Cui, C., & Shen, Y.-Q. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.02.005 · Cited by 736 · see citing works
The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease
Yang, T., Richards, E. M., Pepine, C. J., & Raizada, M. K. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0018-2 · Cited by 753 · see citing works
Kynurenine pathway metabolism and the microbiota-gut-brain axis
Kennedy, P. J., Cryan, J. F., Dinan, T. G., & Clarke, G. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.07.002 · Cited by 724 · see citing works
Self-citation
Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress
Liang, S., Wang, T., Hu, X., Luo, J., Li, W., Wu, X., Duan, Y., & Jin, F. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.09.033 · Cited by 651 · see citing works
Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior
Luczynski, P., McVey Neufeld, K.-A., Oriach, C. S., Clarke, G., Dinan, T. G., & Cryan, J. F. (2016) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw020 · Cited by 632 · see citing works
Fate, activity, and impact of ingested bacteria within the human gut microbiota
Derrien, M., & van Hylckama Vlieg, J. E. T. (2015) · Trends in Microbiology · doi:10.1016/j.tim.2015.03.002 · Cited by 605 · see citing works
Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder
Vuong, H. E., & Hsiao, E. Y. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.08.024 · Cited by 595 · see citing works
Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort
Hill, C. J., Lynch, D. B., Murphy, K., Ulaszewska, M., Jeffery, I. B., O’Shea, C. A., Watkins, C., Dempsey, E., Mattivi, F., Tuohy, K., et al. (2017) · Microbiome · doi:10.1186/s40168-016-0213-y · Cited by 573 · see citing works
Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: a randomized clinical trial
Kazemi, A., Noorbala, A. A., Azam, K., Eskandari, M. H., & Djafarian, K. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.04.010 · Cited by 534 · see citing works
Tryptophan metabolism and gut-brain homeostasis
Roth, W., Zadeh, K., Vekariya, R., Ge, Y., & Mohamadzadeh, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062973 · Cited by 519 · see citing works
Sleep, circadian rhythm, and gut microbiota
Matenchuk, B. A., Mandhane, P. J., & Kozyrskyj, A. L. (2020) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2020.101340 · Cited by 495 · see citing works
Autism Spectrum Disorders and the Gut Microbiota
Fattorusso, A., Di Genova, L., Dell’Isola, G., Mencaroni, E., & Esposito, S. (2019) · Nutrients · doi:10.3390/nu11030521 · Cited by 484 · see citing works
Probiotic Lactobacillus plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: a double-blind, randomized, placebo controlled study
Rudzki, L., Ostrowska, L., Pawlak, D., Małus, A., Pawlak, K., Waszkiewicz, N., & Szulc, A. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.10.010 · Cited by 499 · see citing works
Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease
Kesika, P., Suganthy, N., Sivamaruthi, B. S., & Chaiyasut, C. (2021) · Life Sciences · doi:10.1016/j.lfs.2020.118627 · Cited by 479 · see citing works
Nutritional psychiatry: The present state of the evidence
Marx, W., Moseley, G., Berk, M., & Jacka, F. (2017) · Proceedings of the Nutrition Society · doi:10.1017/s0029665117002026 · Cited by 469 · see citing works
Nutritional psychiatry: Towards improving mental health by what you eat
Adan, R. A. H., van der Beek, E. M., Buitelaar, J. K., Cryan, J. F., Hebebrand, J., Higgs, S., Schellekens, H., & Dickson, S. L. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2019.10.011 · Cited by 454 · see citing works
Self-citation
Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health
Berding, K., Vlckova, K., Marx, W., Schellekens, H., Stanton, C., Clarke, G., Jacka, F., Dinan, T. G., & Cryan, J. F. (2021) · Advances in Nutrition · doi:10.1093/advances/nmaa181 · Cited by 451 · see citing works
Self-citation
Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
Gut microbiome and depression: what we know and what we need to know
Winter, G., Hart, R. A., Charlesworth, R. P. G., & Sharpley, C. F. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0072 · Cited by 394 · see citing works
Gut microbiome diversity is associated with sleep physiology in humans
Smith, R. P., Easson, C., Lyle, S. M., Kapoor, R., Donnelly, C. P., Davidson, E. J., Parikh, E., Lopez, J. V., & Tartar, J. L. (2019) · PLOS ONE · doi:10.1371/journal.pone.0222394 · Cited by 390 · see citing works
The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling
Mazzoli, R., & Pessione, E. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01934 · Cited by 383 · see citing works
Gut-brain Axis and migraine headache: a comprehensive review
On behalf of the School of Advanced Studies of the European Headache Federation (EHF-SAS), Arzani, M., Jahromi, S. R., Ghorbani, Z., Vahabizad, F., Martelletti, P., Ghaemi, A., Sacco, S., & Togha, M. (2020) · The Journal of Headache and Pain · doi:10.1186/s10194-020-1078-9 · Cited by 366 · see citing works
Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice
Guida, F., Turco, F., Iannotta, M., De Gregorio, D., Palumbo, I., Sarnelli, G., Furiano, A., Napolitano, F., Boccella, S., Luongo, L., et al. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.09.001 · Cited by 367 · see citing works
Gut microbiota role in dietary protein metabolism and health-related outcomes: The two sides of the coin
Portune, K. J., Beaumont, M., Davila, A.-M., Tomé, D., Blachier, F., & Sanz, Y. (2016) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2016.08.011 · Cited by 356 · see citing works
Why does the microbiome affect behaviour?
Johnson, K. V.-A., & Foster, K. R. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0014-3 · Cited by 333 · see citing works
Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease
Caputi, V., & Giron, M. C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061689 · Cited by 338 · see citing works
The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology
Doifode, T., Giridharan, V. V., Generoso, J. S., Bhatti, G., Collodel, A., Schulz, P. E., Forlenza, O. V., & Barichello, T. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2020.105314 · Cited by 347 · see citing works
The gut-brain axis: the missing link in depression
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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.
ORCID: O’Mahony, S.M.
Clarke, G.
Dinan, T.G.
Cryan, J.F.
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2015-01
Volume: 277
Pages: 32-48
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2014.07.027
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 · 2014: 5
FWCI: 6.87
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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Serotonin, tryptophan metabolism and the brain-gut-microbiome axis

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