Kynurenine pathway metabolism and the microbiota-gut-brain axis

Kennedy, P.J.; Cryan, J.F.; Dinan, T.G.; Clarke, G.

doi:10.1016/j.neuropharm.2016.07.002

Cited by 724Tryptophan and brain disordersGut microbiota and healthGastrointestinal motility and disorders

Kynurenine pathway metabolism and the microbiota-gut-brain axis

Open access

Kennedy, P.J., Cryan, J.F., Dinan, T.G., Clarke, G.·2017·Neuropharmacology

DOI 10.1016/j.neuropharm.2016.07.002

Open this paper in CoChat — free account

Abstract

It has become increasingly clear that the gut microbiota influences not only gastrointestinal physiology but also central nervous system (CNS) function by modulating signalling pathways of the microbiota-gut-brain axis. Understanding the neurobiological mechanisms underpinning the influence exerted by the gut microbiota on brain function and behaviour has become a key research priority. Microbial regulation of tryptophan metabolism has become a focal point in this regard, with dual emphasis on the regulation of serotonin synthesis and the control of kynurenine pathway metabolism. Here, we focus in detail on the latter pathway and begin by outlining the structural and functional dynamics of the gut microbiota and the signalling pathways of the brain-gut axis. We summarise preclinical and clinical investigations demonstrating that the gut microbiota influences CNS physiology, anxiety, depression, social behaviour, cognition and visceral pain. Pertinent studies are drawn from neurogastroenterology demonstrating the importance of tryptophan and its metabolites in CNS and gastrointestinal function. We outline how kynurenine pathway metabolism may be regulated by microbial control of neuroendocrine function and components of the immune system. Finally, preclinical evidence demonstrating direct and indirect mechanisms by which the gut microbiota can regulate tryptophan availability for kynurenine pathway metabolism, with downstream effects on CNS function, is reviewed. Targeting the gut microbiota represents a tractable target to modulate kynurenine pathway metabolism. Efforts to develop this approach will markedly increase our understanding of how the gut microbiota shapes brain and behaviour and provide new insights towards successful translation of microbiota-gut-brain axis research from bench to bedside. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'.

Integrity signals

Registry

Crossref · 10.1016/j.neuropharm.2016.07.002

Cites

226 of 226 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Under inflammatory conditions, tryptophan metabolism shifts towards increased kynurenine levels, leading to an imbalance in downstream metabolites such as quinolinic acid and kynurenic acid.
“Under inflammatory conditions, tryptophan metabolism shifts towards increased kynurenine levels, leading to an imbalance in its downstream metabolites (TRYCATs), such as quinolinic acid (QUIN) and kynurenic acid (KYNA).”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [72]
In the gut, tryptophan may be metabolized under direct or indirect control by the GM, producing compounds such as serotonin, kynurenines, tryptamine, and indolic compounds that participate in MGB communication.
“In the gut, it may be further metabolized under direct or indirect control by the GM, giving rise to several compounds, such as serotonin, kynurenines, tryptamine, and indolic compounds, which participate in MGB communication (197, 198).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [198]
Kynurenine can pass the blood-brain barrier and has been shown to produce neuroinflammation and neurodegeneration, which have also been reported in AD and depression.
“Kynurenine, which can pass the blood-brain barrier, has been shown to produce neuroinflammation and neurodegeneration, which have also been reported in AD and depression [31].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [31]
Many of these differences can be driven by a unique metabolic profile of each bacterial genus, including the production of different biologically active compounds, such as SCFAs or indoles.
“Many of these differences can be driven by a unique metabolic profile of each bacterial genus, including the production of different biologically active compounds, such as SCFAs or indoles (Kennedy et al., 2017; Sandhu et al., 2017).”
From Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism (2017) · cites this paper as Kennedy et al., 2017
More than 90% of tryptophan is catabolized down to kynurenine in the liver, with liver Tdo2 activity determining systemic kynurenine levels and tryptophan availability for the brain.
“Indeed, > 90% of tryptophan is catabolized down to kynurenine in the liver, with liver Tdo2 activity determining the systemic levels of kynurenine, and the availability of tryptophan for the brain (Kennedy et al., 2017).”
From Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism (2017) · cites this paper as Kennedy et al., 2017

Structure, function and diversity of the healthy human microbiome
The Human Microbiome Project Consortium (2012) · Nature · doi:10.1038/nature11234 · Cited by 11,726 · see citing works
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
Kawai, T., & Akira, S. (2010) · Nature Immunology · doi:10.1038/ni.1863 · Cited by 9,304 · see citing works
The human microbiome project
Turnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C. M., Knight, R., & Gordon, J. I. (2007) · Nature · doi:10.1038/nature06244 · Cited by 6,091 · see citing works
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 · see citing works
The gut microbiota shapes intestinal immune responses during health and disease
Round, J. L., & Mazmanian, S. K. (2009) · Nature Reviews Immunology · doi:10.1038/nri2515 · Cited by 5,029 · see citing works
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 · see citing works
Self-citation
Interactions Between the Microbiota and the Immune System
Hooper, L. V., Littman, D. R., & Macpherson, A. J. (2012) · Science · doi:10.1126/science.1223490 · Cited by 4,173 · see citing works
Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve
Bravo, 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 · see citing works
Self-citation
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
Host microbiota constantly control maturation and function of microglia in the CNS
Erny, D., Hrabě de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4030 · Cited by 3,569 · see citing works
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 · see citing works
Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders
Hsiao, E. Y., McBride, S. W., Hsien, S., Sharon, G., Hyde, E. R., McCue, T., Codelli, J. A., Chow, J., Reisman, S. E., Petrosino, J. F., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.024 · Cited by 3,283 · see citing works
Normal gut microbiota modulates brain development and behavior
Heijtz, R. D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., Hibberd, M. L., Forssberg, H., & Pettersson, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010529108 · Cited by 3,228 · see citing works
Neurobiology of Depression
Nestler, E. J., Barrot, M., DiLeone, R. J., Eisch, A. J., Gold, S. J., & Monteggia, L. M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00653-0 · Cited by 3,217 · see citing works
Development of the Human Infant Intestinal Microbiota
Palmer, C., Bik, E. M., DiGiulio, D. B., Relman, D. A., & Brown, P. O. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050177 · Cited by 2,877 · see citing works
The gut flora as a forgotten organ
O'Hara, A. M., & Shanahan, F. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400731 · Cited by 2,791 · see citing works
Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice
Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X., Kubo, C., & Koga, Y. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.063388 · Cited by 2,735 · see citing works
Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites
Wikoff, W. R., Anfora, A. T., Liu, J., Schultz, P. G., Lesley, S. A., Peters, E. C., & Siuzdak, G. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812874106 · Cited by 2,677 · see citing works
The gut microbiota influences blood-brain barrier permeability in mice
Braniste, V., Al-Asmakh, M., Kowal, C., Anuar, F., Abbaspour, A., Tóth, M., Korecka, A., Bakocevic, N., Ng, L. G., Kundu, P., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009759 · Cited by 2,530 · see citing works
Population-level analysis of gut microbiome variation
Falony, G., Joossens, M., Vieira-Silva, S., Wang, J., Darzi, Y., Faust, K., Kurilshikov, A., Bonder, M. J., Valles-Colomer, M., Vandeputte, D., et al. (2016) · Science · doi:10.1126/science.aad3503 · Cited by 2,400 · see citing works
Altered fecal microbiota composition in patients with major depressive disorder
Jiang, H., Ling, Z., Zhang, Y., Mao, H., Ma, Z., Yin, Y., Wang, W., Tang, W., Tan, Z., Shi, J., et al. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.03.016 · Cited by 2,275 · see citing works
Factors influencing the composition of the intestinal microbiota in early infancy
Penders, J., Thijs, C., Vink, C., Stelma, F. F., Snijders, B., Kummeling, I., van den Brandt, P. A., & Stobberingh, E. E. (2006) · PEDIATRICS · doi:10.1542/peds.2005-2824 · Cited by 2,232 · see citing works
The role of the gut microbiota in nutrition and health
Flint, H. J., Scott, K. P., Louis, P., & Duncan, S. H. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.156 · Cited by 2,203 · see citing works
The expanded biology of serotonin
Berger, M., Gray, J. A., & Roth, B. L. (2009) · Annual Review of Medicine · doi:10.1146/annurev.med.60.042307.110802 · Cited by 2,100 · see citing works
Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism
Zheng, P., Zeng, B., Zhou, C., Liu, M., Fang, Z., Xu, X., Zeng, L., Chen, J., Fan, S., Du, X., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.44 · Cited by 2,023 · see citing works
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 · Cited by 2,012 · see citing works
Self-citation
Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity
Zhernakova, A., Kurilshikov, A., Bonder, M. J., Tigchelaar, E. F., Schirmer, M., Vatanen, T., Mujagic, Z., Vila, A. V., Falony, G., Vieira-Silva, S., et al. (2016) · Science · doi:10.1126/science.aad3369 · Cited by 1,914 · see citing works
An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor
Opitz, C. A., Litzenburger, U. M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T., Jestaedt, L., Schrenk, D., Weller, M., et al. (2011) · Nature · doi:10.1038/nature10491 · Cited by 1,898 · see citing works
The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner
Clarke, G., Grenham, S., Scully, P., Fitzgerald, P., Moloney, R. D., Shanahan, F., Dinan, T. G., & Cryan, J. F. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.77 · Cited by 1,893 · see citing works
Self-citation
Composition, variability, and temporal stability of the intestinal microbiota of the elderly
Claesson, M. J., Cusack, S., O'Sullivan, O., Greene-Diniz, R., de Weerd, H., Flannery, E., Marchesi, J. R., Falush, D., Dinan, T., Fitzgerald, G., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000097107 · Cited by 1,754 · see citing works
Self-citation
The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice
Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J., Deng, Y., Blennerhassett, P., Macri, J., McCoy, K. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.04.052 · Cited by 1,748 · see citing works
Diet-induced extinctions in the gut microbiota compound over generations
Sonnenburg, E. D., Smits, S. A., Tikhonov, M., Higginbottom, S. K., Wingreen, N. S., & Sonnenburg, J. L. (2016) · Nature · doi:10.1038/nature16504 · Cited by 1,730 · see citing works
The enteric nervous system and neurogastroenterology
Furness, J. B. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.32 · Cited by 1,619 · see citing works
The Shikimate Pathway and Aromatic Amino Acid Biosynthesis in Plants
Maeda, H. A., & Dudareva, N. (2012) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-042811-105439 · Cited by 1,568 · see citing works
The serotonin signaling system: from basic understanding to drug development for functional GI disorders
Gershon, M. D., & Tack, J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2006.11.002 · Cited by 1,563 · see citing works
Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor
Rothhammer, V., Mascanfroni, I. D., Bunse, L., Takenaka, M. C., Kenison, J. E., Mayo, L., Chao, C.-C., Patel, B., Yan, R., Blain, M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4106 · Cited by 1,559 · see citing works
Kynurenines in the mammalian brain: when physiology meets pathology
Schwarcz, R., Bruno, J. P., Muchowski, P. J., & Wu, H.-Q. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3257 · Cited by 1,530 · see citing works
CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands
Lamas, B., Richard, M. L., Leducq, V., Pham, H.-P., Michel, M.-L., Da Costa, G., Bridonneau, C., Jegou, S., Hoffmann, T. W., Natividad, J. M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4102 · Cited by 1,482 · see citing works
Reduced anxiety-like behavior and central neurochemical change in germ-free mice: Behavior in germ-free mice
Neufeld, K. M., Kang, N., Bienenstock, J., & Foster, J. A. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2010.01620.x · Cited by 1,392 · see citing works
Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells
Reigstad, C. S., Salmonson, C. E., III, J. F. R., Szurszewski, J. H., Linden, D. R., Sonnenburg, J. L., Farrugia, G., & Kashyap, P. C. (2015) · The FASEB Journal · doi:10.1096/fj.14-259598 · Cited by 1,335 · see citing works
Assessment of psychotropic-like properties of a probiotic formulation ( Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects
Messaoudi, M., Lalonde, R., Violle, N., Javelot, H., Desor, D., Nejdi, A., Bisson, J.-F., Rougeot, C., Pichelin, M., Cazaubiel, M., et al. (2011) · British Journal of Nutrition · doi:10.1017/s0007114510004319 · Cited by 1,324 · see citing works
The composition of the gut microbiota throughout life, with an emphasis on early life
Rodríguez, J. M., Murphy, K., Stanton, C., Ross, R. P., Kober, O. I., Juge, N., Avershina, E., Rudi, K., Narbad, A., Jenmalm, M. C., et al. (2015) · Microbial Ecology in Health and Disease · doi:10.3402/mehd.v26.26050 · Cited by 1,320 · see citing works
Psychobiotics: A novel class of psychotropic
Dinan, T. G., Stanton, C., & Cryan, J. F. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.05.001 · Cited by 1,287 · see citing works
Self-citation
Minireview: Gut microbiota: The neglected endocrine organ
Clarke, G., Stilling, R. M., Kennedy, P. J., Stanton, C., Cryan, J. F., & Dinan, T. G. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1108 · Cited by 1,192 · see citing works
Self-citation
Consumption of fermented milk product with probiotic modulates brain activity
Tillisch, K., Labus, J., Kilpatrick, L., Jiang, Z., Stains, J., Ebrat, B., Guyonnet, D., Legrain–Raspaud, S., Trotin, B., Naliboff, B., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.02.043 · Cited by 1,192 · see citing works
Serotonin signalling in the gut: functions, dysfunctions and therapeutic targets
Mawe, G. M., & Hoffman, J. M. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.105 · Cited by 1,165 · see citing works
Exposure to a social stressor alters the structure of the intestinal microbiota: Implications for stressor-induced immunomodulation
Bailey, M. T., Dowd, S. E., Galley, J. D., Hufnagle, A. R., Allen, R. G., & Lyte, M. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.10.023 · Cited by 1,123 · 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
Microbiota and neurodevelopmental windows: implications for brain disorders
Borre, Y. E., O’Keeffe, G. W., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.05.002 · Cited by 1,089 · see citing works
Self-citation
Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses
O'Mahony, S. M., Marchesi, J. R., Scully, P., Codling, C., Ceolho, A.-M., Quigley, E. M. M., Cryan, J. F., & Dinan, T. G. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.06.026 · Cited by 1,069 · see citing works
Self-citation
Indole as an intercellular signal in microbial communities
Lee, J.-H., & Lee, J. (2010) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2009.00204.x · Cited by 1,059 · see citing works
Correlation between the human fecal microbiota and depression
Naseribafrouei, A., Hestad, K., Avershina, E., Sekelja, M., Linløkken, A., Wilson, R., & Rudi, K. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12378 · Cited by 1,044 · see citing works
Gut microbes and the brain: paradigm shift in neuroscience
Mayer, E. A., Knight, R., Mazmanian, S. K., Cryan, J. F., & Tillisch, K. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3299-14.2014 · Cited by 1,033 · see citing works
Self-citation
The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat
Desbonnet, L., Garrett, L., Clarke, G., Bienenstock, J., & Dinan, T. G. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2008.03.009 · Cited by 952 · see citing works
Self-citation
Bacterial infection causes stress-induced memory dysfunction in mice
Gareau, M. G., Wine, E., Rodrigues, D. M., Cho, J. H., Whary, M. T., Philpott, D. J., MacQueen, G., & Sherman, P. M. (2011) · Gut · doi:10.1136/gut.2009.202515 · Cited by 909 · cited 2× · see citing works
“Preclinical studies utilising various strategies including GF and GI infection models (Gareau, 2014; Gareau et al., 2011), antibiotic treatment (Desbonnet et al., 2015; Fröhlich et al., 2016) dietary manipulation (Li et al., 2009; Ohland et al., 2013) and probiotic treatment (Davari et al., 2013;…”
Method
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
The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation
Bansal, T., Alaniz, R. C., Wood, T. K., & Jayaraman, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906112107 · Cited by 868 · see citing works
Microbiota is essential for social development in the mouse
Desbonnet, L., Clarke, G., Shanahan, F., Dinan, T. G., & Cryan, J. F. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.65 · Cited by 866 · see citing works
Self-citation
An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid
Perkins, M. N., & Stone, T. W. (1982) · Brain Research · doi:10.1016/0006-8993(82)91048-4 · Cited by 849 · see citing works
Endogenous kynurenines as targets for drug discovery and development
Stone, T. W., & Darlington, L. G. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd870 · Cited by 768 · see citing works
Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour
Desbonnet, L., Clarke, G., Traplin, A., O’Sullivan, O., Crispie, F., Moloney, R. D., Cotter, P. D., Dinan, T. G., & Cryan, J. F. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.04.004 · Cited by 760 · see citing works
Self-citation
Quinolinic acid: a potent endogenous excitant at amino acid receptors in CNS
Stone, T. W., & Perkins, M. N. (1981) · European Journal of Pharmacology · doi:10.1016/0014-2999(81)90587-2 · Cited by 751 · see citing works
Cognitive impairment by antibiotic-induced gut dysbiosis: analysis of gut microbiota-brain communication
Fröhlich, E. E., Farzi, A., Mayerhofer, R., Reichmann, F., Jačan, A., Wagner, B., Zinser, E., Bordag, N., Magnes, C., Fröhlich, E., et al. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.02.020 · Cited by 720 · see citing works
Aryl hydrocarbon receptor control of a disease tolerance defence pathway
Bessede, A., Gargaro, M., Pallotta, M. T., Matino, D., Servillo, G., Brunacci, C., Bicciato, S., Mazza, E. M. C., Macchiarulo, A., Vacca, C., et al. (2014) · Nature · doi:10.1038/nature13323 · Cited by 676 · see citing works
Chronic Gastrointestinal Inflammation Induces Anxiety-Like Behavior and Alters Central Nervous System Biochemistry in Mice
Bercik, P., Verdu, E. F., Foster, J. A., Macri, J., Potter, M., Huang, X., Malinowski, P., Jackson, W., Blennerhassett, P., Neufeld, K. A., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.06.063 · Cited by 674 · see citing works
A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood
Steenbergen, L., Sellaro, R., van Hemert, S., Bosch, J. A., & Colzato, L. S. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.04.003 · Cited by 671 · cited 1× · see citing works
“Emerging data in healthy humans support preclinical findings suggesting the gut microbiota influence mood and anxiety (Benton et al., 2007; Messaoudi et al., 2011; Steenbergen et al., 2015).”
Background
Brain–Gut Interactions in Inflammatory Bowel Disease
Bonaz, B. L., & Bernstein, C. N. (2013) · Gastroenterology · doi:10.1053/j.gastro.2012.10.003 · Cited by 667 · see citing works
Establishment of the gut microbiota in Western infants
Adlerberth, I., & Wold, A. E. (2009) · Acta Paediatrica · doi:10.1111/j.1651-2227.2008.01060.x · Cited by 665 · see citing works
Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism
Malkova, N. V., Yu, C. Z., Hsiao, E. Y., Moore, M. J., & Patterson, P. H. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.01.011 · Cited by 662 · see citing works
Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis
Stilling, R. M., Dinan, T. G., & Cryan, J. F. (2014) · Genes, Brain and Behavior · doi:10.1111/gbb.12109 · Cited by 637 · see citing works
Regulation of prefrontal cortex myelination by the microbiota
Hoban, A. E., Stilling, R. M., Ryan, F. J., Shanahan, F., Dinan, T. G., Claesson, M. J., Clarke, G., & Cryan, J. F. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.42 · Cited by 635 · see citing works
Self-citation
Regulation of the stress response by the gut microbiota: implications for psychoneuroendocrinology
Dinan, T. G., & Cryan, J. F. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.03.007 · Cited by 577 · see citing works
Self-citation
Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook
Kelly, C. R., Kahn, S., Kashyap, P., Laine, L., Rubin, D., Atreja, A., Moore, T., & Wu, G. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.05.008 · Cited by 572 · see citing works
Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition
Wong, M.-L., Inserra, A., Lewis, M. D., Mastronardi, C. A., Leong, L., Choo, J., Kentish, S., Xie, P., Morrison, M., Wesselingh, S. L., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.46 · Cited by 568 · see citing works
Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials
Kristensen, N. B., Bryrup, T., Allin, K. H., Nielsen, T., Hansen, T. H., & Pedersen, O. (2016) · Genome Medicine · doi:10.1186/s13073-016-0300-5 · Cited by 561 · cited 1× · see citing works
“However, a recent meta-analysis suggests that probiotics alonemay not be sufficient to significantly change the gut microbial composition (Kristensen et al., 2016).”
Result
Manipulation of Brain Kynurenines: Glial Targets, Neuronal Effects, and Clinical Opportunities
Schwarcz, R. M., & Pellicciari, R. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.034439 · Cited by 556 · see citing works
Impact of consuming a milk drink containing a probiotic on mood and cognition
Benton, D., Williams, C., & Brown, A. (2007) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602546 · Cited by 554 · see citing works
The serotonin system in autism spectrum disorder: From biomarker to animal models
Muller, C. L., Anacker, A. M. J., & Veenstra-VanderWeele, J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.11.010 · Cited by 531 · see citing works
Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers
Schmidt, K., Cowen, P. J., Harmer, C. J., Tzortzis, G., Errington, S., & Burnet, P. W. J. (2015) · Psychopharmacology · doi:10.1007/s00213-014-3810-0 · Cited by 522 · see citing works
Tryptophan metabolism in the central nervous system: medical implications
Ruddick, J. P., Evans, A. K., Nutt, D. J., Lightman, S. L., Rook, G. A. W., & Lowry, C. A. (2006) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399406000068 · Cited by 519 · see citing works
Roles of indole as an interspecies and interkingdom signaling molecule
Lee, J.-H., Wood, T. K., & Lee, J. (2015) · Trends in Microbiology · doi:10.1016/j.tim.2015.08.001 · Cited by 516 · see citing works
Adult hippocampal neurogenesis is regulated by the microbiome
Ogbonnaya, E. S., Clarke, G., Shanahan, F., Dinan, T. G., Cryan, J. F., & O’Leary, O. F. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.12.023 · Cited by 491 · see citing works
Self-citation
Pattern recognition receptors and central nervous system repair
Kigerl, K. A., de Rivero Vaccari, J. P., Dietrich, W. D., Popovich, P. G., & Keane, R. W. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.01.001 · Cited by 490 · see citing works
A Meta-Analysis of Probiotic Efficacy for Gastrointestinal Diseases
Ritchie, M. L., & Romanuk, T. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034938 · Cited by 474 · see citing works
Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation
Gareau, M. G., Jury, J., MacQueen, G., Sherman, P. M., & Perdue, M. H. (2007) · Gut · doi:10.1136/gut.2006.117176 · Cited by 472 · see citing works
Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis
Möhle, L., Mattei, D., Heimesaat, M. M., Bereswill, S., Fischer, A., Alutis, M., French, T., Hambardzumyan, D., Matzinger, P., Dunay, I. R., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.074 · Cited by 470 · see citing works
Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis
Crane, J., Palanivel, R., Mottillo, E., Bujak, A. L., Wang, H.-Q., Ford, R., Collins, A., Blümer, R., Fullerton, M., Yabut, J. M., et al. (2014) · Nature Medicine · doi:10.1038/nm.3766 · Cited by 462 · see citing works
Maternal prenatal stress is associated with the infant intestinal microbiota
Zijlmans, M. A. C., Korpela, K., Riksen-Walraven, J. M., de Vos, W. M., & de Weerth, C. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.01.006 · Cited by 438 · see citing works
Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice
Ball, H. J., Sánchez-Pérez, Á., Weiser, S., Austin, C., Astelbauer, F., Miu, J., McQuillan, J. A., Stocker, R., Jermiin, L. S., & Hunt, N. H. (2007) · Gene · doi:10.1016/j.gene.2007.04.010 · Cited by 433 · see citing works
<scp>B</scp> ifidobacteria exert strain‐specific effects on stress‐related behavior and physiology in <scp>BALB</scp> /c mice
Savignac, H. M., Kiely, B., Dinan, T. G., & Cryan, J. F. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12427 · Cited by 418 · see citing works
Antidepressant binding site in a bacterial homologue of neurotransmitter transporters
Singh, S. K., Yamashita, A., & Gouaux, E. (2007) · Nature · doi:10.1038/nature06038 · Cited by 414 · see citing works
Kynurenines in CNS disease: regulation by inflammatory cytokines.
Campbell, B. M., Charych, E., Lee, A. W., & Möller, T. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00012 · Cited by 409 · see citing works
A prospective population-based study of triggers of symptomatic flares in IBD
Bernstein, C. N., Singh, S., Graff, L. A., Walker, J. R., Miller, N., & Cheang, M. (2010) · American Journal of Gastroenterology · doi:10.1038/ajg.2010.140 · Cited by 400 · see citing works
Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota
Galley, J. D., Nelson, M. C., Yu, Z., Dowd, S. E., Walter, J., Kumar, P., Lyte, M., & Bailey, M. T. (2014) · BMC Microbiology · doi:10.1186/1471-2180-14-189 · Cited by 398 · see citing works
Stress and the Microbiota–Gut–Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome
Moloney, R. D., Johnson, A. C., O’Mahony, S. M., Dinan, T. G., Meerveld, B. G., & Cryan, J. F. (2015) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12490 · Cited by 396 · see citing works
Self-citation
Rethinking “Enterotypes”
Knights, D., Ward, T. L., McKinlay, C. E., Miller, H., Gonzalez, A., McDonald, D., & Knight, R. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.09.013 · Cited by 396 · see citing works
The gut microbiota modulates host amino acid and glutathione metabolism in mice
Mardinoglu, A., Shoaie, S., Bergentall, M., Ghaffari, P., Zhang, C., Larsson, E., Bäckhed, F., & Nielsen, J. (2015) · Molecular Systems Biology · doi:10.15252/msb.20156487 · Cited by 383 · see citing works
Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles
Hubbard, T. D., Murray, I. A., Bisson, W. H., Lahoti, T. S., Gowda, K., Amin, S. G., Patterson, A. D., & Perdew, G. H. (2015) · Scientific Reports · doi:10.1038/srep12689 · Cited by 377 · see citing works
Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine
Savignac, H. M., Corona, G., Mills, H., Chen, L., Spencer, J. P. E., Tzortzis, G., & Burnet, P. W. J. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2013.10.006 · Cited by 377 · see citing works
Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function
Keszthelyi, D., Troost, F. J., & Masclee, A. (2009) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2009.01370.x · Cited by 369 · see citing works
The Handbook of Child and Adolescent Clinical Psychology
Carr, A. (2015) · Routledge eBooks · doi:10.4324/9781315744230 · Cited by 362 · see citing works
Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans
Palego, L., Betti, L., Rossi, A., & Giannaccini, G. (2016) · Journal of Amino Acids · doi:10.1155/2016/8952520 · Cited by 349 · see citing works
Segmented Filamentous Bacteria Are Indigenous Intestinal Bacteria That Activate Intraepithelial Lymphocytes and Induce MHC Class II Molecules and Fucosyl Asialo GM1 Glycolipids on the Small Intestinal Epithelial Cells in the Ex‐Germ‐Free Mouse
Umesaki, Y., Okada, Y., Matsumoto, S., Imaoka, A., & Setoyama, H. (1995) · Microbiology and Immunology · doi:10.1111/j.1348-0421.1995.tb02242.x · Cited by 346 · see citing works
Irritable bowel syndrome: A microbiome-gut-brain axis disorder?
Kennedy, P. J. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i39.14105 · Cited by 335 · see citing works
Self-citation
Erratum to: Clinical metagenomic identification of Balamuthia mandrillaris encephalitis and assembly of the draft genome: the continuing case for reference genome sequencing
Greninger, A. L., Messacar, K., Dunnebacke, T. H., Naccache, S. N., Federman, S., Bouquet, J., Mirsky, D. M., Nomura, Y., Yagi, S., Glaser, C. A., et al. (2016) · Genome Medicine · doi:10.1186/s13073-015-0257-9 · Cited by 333 · see citing works
Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain
Jašarević, E., Howerton, C. L., Howard, C. D., & Bale, T. L. (2015) · Endocrinology · doi:10.1210/en.2015-1177 · Cited by 329 · see citing works
Brain-gut axis in health and disease
Aziz, Q., & Thompson, D. G. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70540-2 · Cited by 328 · see citing works
Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior
Gacias, M., Gaspari, S., Santos, P.-M. G., Tamburini, S., Andrade, M., Zhang, F., Shen, N., Tolstikov, V., Kiebish, M. A., Dupree, J. L., et al. (2016) · eLife · doi:10.7554/elife.13442 · Cited by 308 · see citing works
Structural & functional consequences of chronic psychosocial stress on the microbiome & host
Bharwani, A., Mian, M. F., Foster, J. A., Surette, M. G., Bienenstock, J., & Forsythe, P. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.10.001 · Cited by 293 · see citing works
Food, immunity, and the microbiome
Tilg, H., & Moschen, A. R. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.12.036 · Cited by 292 · see citing works
Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome–gut–brain axis
Davari, S., Talaei, S. A., Alaei, H., & salami, M. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.02.055 · Cited by 290 · cited 2× · see citing works
“…al., 2011), antibiotic treatment (Desbonnet et al., 2015; Fröhlich et al., 2016) dietary manipulation (Li et al., 2009; Ohland et al., 2013) and probiotic treatment (Davari et al., 2013; Ohland et al., 2013), have found that cognitive function is influenced by the composition of the gut microbiota.”
Background
Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood
Golubeva, A. V., Crampton, S., Desbonnet, L., Edge, D., O'Sullivan, O., Lomasney, K. W., Zhdanov, A. V., Crispie, F., Moloney, R. D., Borre, Y. E., et al. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.06.002 · Cited by 283 · see citing works
Self-citation
Effects of Lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome
Ohland, C. L., Kish, L., Bell, H., Thiesen, A., Hotte, N., Pankiv, E., & Madsen, K. L. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.02.008 · Cited by 273 · see citing works
The kynurenine pathway as a therapeutic target in cognitive and neurodegenerative disorders
Stone, T. W., & Darlington, L. G. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12230 · Cited by 272 · see citing works
Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats
O’Mahony, S. M., Felice, V. D., Nally, K., Savignac, H. M., Claesson, M. J., Scully, P., Woznicki, J., Hyland, N. P., Shanahan, F., Quigley, E. M., et al. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.07.054 · Cited by 272 · see citing works
Self-citation
The impact of gut microbiota on brain and behaviour
Dinan, T. G., & Cryan, J. F. (2015) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000221 · Cited by 267 · see citing works
Self-citation
Effects of tryptophan loading on human cognition, mood, and sleep
Silber, B. Y., & Schmitt, J. A. J. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.08.005 · Cited by 260 · see citing works
Antimicrobial activity of psychotropic drugs
Munoz-Bellido, J. L., Munoz-Criado, S., & Garcı̀a-Rodrı̀guez, J. A. (2000) · International Journal of Antimicrobial Agents · doi:10.1016/s0924-8579(99)00154-5 · Cited by 249 · see citing works
Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice
Aidy, S. E., van Baarlen, P., Derrien, M., Lindenbergh-Kortleve, D. J., Hooiveld, G. J. E. J., Levenez, F., Dore, J. M., Dekker, J. P., Samsom, J. N., Nieuwenhuis, E. E. S., et al. (2012) · Mucosal Immunology · doi:10.1038/mi.2012.32 · Cited by 249 · see citing works
Memory and learning behavior in mice is temporally associated with diet-induced alterations in gut bacteria
Li, W., Dowd, S. E., Scurlock, B., Acosta-Martinez, V., & Lyte, M. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.12.004 · Cited by 246 · see citing works
Serotonin and GI clinical disorders
Spiller, R. E. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.016 · Cited by 234 · see citing works
Microbes & neurodevelopment – Absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala
Stilling, R. M., Ryan, F. J., Hoban, A. E., Shanahan, F., Clarke, G., Claesson, M. J., Dinan, T. G., & Cryan, J. F. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.07.009 · Cited by 233 · see citing works
Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice
Reber, S. O., Siebler, P. H., Donner, N. C., Morton, J. T., Smith, D. G., Kopelman, J. M., Lowe, K. R., Wheeler, K. J., Fox, J. H., Hassell, J. E., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600324113 · Cited by 233 · see citing works
NAD Biosynthesis
Kurnasov, O. V., Goral, V. N., Colabroy, K. L., Gerdes, S., Anantha, S., Osterman, A. L., & Begley, T. P. (2003) · Chemistry & Biology · doi:10.1016/j.chembiol.2003.11.011 · Cited by 230 · see citing works
Ghrelin signalling and obesity: At the interface of stress, mood and food reward
Schellekens, H., Finger, B. C., Dinan, T. G., & Cryan, J. F. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.06.004 · Cited by 229 · see citing works
Self-citation
Tryptophan availability for kynurenine pathway metabolism across the life span: Control mechanisms and focus on aging, exercise, diet and nutritional supplements
Badawy, A. A. ‐. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.11.015 · Cited by 228 · see citing works
Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-β levels in male mice
Savignac, H. M., Couch, Y., Stratford, M., Bannerman, D. M., Tzortzis, G., Anthony, D. C., & Burnet, P. W. J. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.10.007 · Cited by 223 · see citing works
Ontogeny of the N-Methyl-D-Aspartate (NMDA) Receptor System and Susceptibility to Neurotoxicity
Haberny, K. A. (2002) · Toxicological Sciences · doi:10.1093/toxsci/68.1.9 · Cited by 218 · see citing works
Review article: probiotics for the treatment of irritable bowel syndrome – focus on lactic acid bacteria
Clarke, G. A., Cryan, J. F., Dinan, T. G., & Quigley, E. M. M. (2012) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2011.04965.x · Cited by 217 · see citing works
Self-citation
Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication
El Aidy, S., Dinan, T. G., & Cryan, J. F. (2015) · Clinical Therapeutics · doi:10.1016/j.clinthera.2015.03.002 · Cited by 215 · see citing works
Self-citation
The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications
Collins, S. M., Kassam, Z., & Berčík, P. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.06.004 · Cited by 206 · see citing works
Biosynthetic Manipulation of Tryptophan in Bacteria: Pathways and Mechanisms
Alkhalaf, L. M., & Ryan, K. S. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2015.02.005 · Cited by 206 · see citing works
The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat
McKernan, D. P., Fitzgerald, P., Dinan, T. G., & Cryan, J. F. (2010) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2010.01520.x · Cited by 205 · see citing works
Self-citation
Tryptophan metabolism, disposition and utilization in pregnancy
Badawy, A. A.-B. (2015) · Bioscience Reports · doi:10.1042/bsr20150197 · Cited by 205 · see citing works
Brain imaging approaches to the study of functional GI disorders: A Rome Working Team Report
Mayer, E. A., Aziz, Q., Coen, S., Kern, M., Labus, J. S., Lane, R., Kuo, B., Naliboff, B., & Tracey, I. (2009) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2009.01304.x · Cited by 204 · see citing works
Early-life adversity and brain development: Is the microbiome a missing piece of the puzzle?
O’Mahony, S. M., Clarke, G., Dinan, T. G., & Cryan, J. F. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2015.09.068 · Cited by 203 · see citing works
Self-citation
Host microbiota modulates development of social preference in mice
Arentsen, T., Raith, H., Qian, Y., Forssberg, H., & Heijtz, R. D. (2015) · Microbial Ecology in Health and Disease · doi:10.3402/mehd.v26.29719 · Cited by 202 · see citing works
Factors affecting health related quality of life of patients with inflammatory bowel disease
Casellas, F., López-Vivancos, J., Casado, A., & Malagelada, J. (2002) · Quality of Life Research · doi:10.1023/a:1020841601110 · Cited by 198 · see citing works
Microbiota-gut-brain axis and cognitive function
Gareau, M. G. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_16 · Cited by 189 · see citing works
Irritable bowel syndrome: towards biomarker identification
Clarke, G. A., Quigley, E. M. M., Cryan, J. F., & Dinan, T. G. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.08.001 · Cited by 180 · see citing works
Self-citation
Priming for health: gut microbiota acquired in early life regulates physiology, brain and behaviour
Clarke, G., O'Mahony, S., Dinan, T., & Cryan, J. (2014) · Acta Paediatrica · doi:10.1111/apa.12674 · Cited by 179 · see citing works
Self-citation
Fermented milk of Lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adults
Chung, Y.-C., Jin, H.-M., Cui, Y., Kim, D. S., Jung, J. M., Park, J.-I., Jung, E.-S., Choi, E.-K., & Chae, S.-W. (2014) · Journal of Functional Foods · doi:10.1016/j.jff.2014.07.007 · Cited by 173 · see citing works
Manipulation of the Microbiota for Treatment of IBS and IBD—Challenges and Controversies
Shanahan, F., & Quigley, E. M. M. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.01.050 · Cited by 172 · cited 2× · see citing works
“There is much interest in the minute regarding the possible wider application of faecal microbiota transplant beyond its use for the treatment of Clostridium difficile infection (Kelly et al., 2015a; Shanahan and Quigley, 2014).”
Background
Selective effects of serotonergic psychoactive agents on gastrointestinal functions in health.
Chial, H., Camilleri, M., Burton, D., Thomforde, G., Olden, K., & Stephens, D. (2003) · American Journal of Physiology - Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00266.2002 · Cited by 169 · see citing works
Stress-Induced Visceral Pain: Toward Animal Models of Irritable-Bowel Syndrome and Associated Comorbidities
Moloney, R. D., O’Mahony, S. M., Dinan, T. G., & Cryan, J. F. (2015) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2015.00015 · Cited by 167 · see citing works
Self-citation
5-HT1A and beyond: the role of serotonin and its receptors in depression and the antidepressant response
Cryan, J. F., & Leonard, B. E. (2000) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/(sici)1099-1077(200003)15:2 · Cited by 164 · see citing works
Self-citation
Genetic and Hormonal Regulation of Tryptophan–Kynurenine Metabolism
Oxenkrug, G. F. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1403.003 · Cited by 163 · see citing works
Indoleamine 2,3-dioxygenase 2 (IDO2) and the kynurenine pathway: characteristics and potential roles in health and disease
Fatokun, A. A., Hunt, N. H., & Ball, H. J. (2013) · Amino Acids · doi:10.1007/s00726-013-1602-1 · Cited by 162 · see citing works
Stress-related regulation of the kynurenine pathway: Relevance to neuropsychiatric and degenerative disorders
O’Farrell, K., & Harkin, A. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.12.004 · Cited by 161 · see citing works
Lactobacillus johnsonii inhibits indoleamine 2,3‐dioxygenase and alters tryptophan metabolite levels in BioBreeding rats
Valladares, R. B., Bojilova, L., Potts, A. H., Cameron, E., Gardner, C. L., Lorca, G. L., & González, C. F. (2013) · The FASEB Journal · doi:10.1096/fj.12-223339 · Cited by 156 · see citing works
Serotonin and the regulation of mammalian energy balance
Donovan, M. H., & Tecott, L. H. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00036 · Cited by 150 · see citing works
IL-8 and IDO Expression by Human Gingival Fibroblasts via TLRs
Mahanonda, R., Sa‐Ard‐Iam, N., Montreekachon, P., Pimkhaokham, A., Yongvanitchit, K., Fukuda, M. M., & Pichyangkul, S. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.2.1151 · Cited by 147 · see citing works
The handbook of child and adolescent clinical psychology: a contextual approach
(2000) · Choice Reviews Online · doi:10.5860/choice.37-4858 · Cited by 145 · see citing works
RNA-based regulation of genes of tryptophan synthesis and degradation, in bacteria
Yanofsky, C. (2007) · RNA · doi:10.1261/rna.620507 · Cited by 144 · see citing works
The biosynthesis of nicotinamide adenine dinucleotides in bacteria
Begley, T. P., Kinsland, C. L., Mehl, R. A., Osterman, A. L., & Dorrestein, P. C. (2001) · Vitamins and hormones · doi:10.1016/s0083-6729(01)61003-3 · Cited by 143 · see citing works
Feeding the brain and nurturing the mind: linking nutrition and the gut microbiota to brain development
Goyal, M. S., Venkatesh, S., Milbrandt, J., Gordon, J. I., & Raichle, M. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1511465112 · Cited by 141 · see citing works
Review article: modulation of the brain–gut axis as a therapeutic approach in gastrointestinal disease
Mayer, E. A., Tillisch, K., & Bradesi, S. (2006) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2006.03078.x · Cited by 139 · see citing works
Aerobic tryptophan degradation pathway in bacteria: novel kynurenine formamidase
Kurnasov, O. V., Jablonski, L. M., Polanuyer, B. M., et al. (2003) · FEMS Microbiology Letters · doi:10.1016/s0378-1097(03)00684-0 · Cited by 138 · see citing works
Adding fuel to the fire: the impact of stress on the ageing brain
Prenderville, J. A., Kennedy, P. J., Dinan, T. G., & Cryan, J. F. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2014.11.001 · Cited by 136 · see citing works
Self-citation
Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort
Clarke, G., Fitzgerald, P., Cryan, J., Cassidy, E., Quigley, E., & Dinan, T. (2009) · BMC Gastroenterology · doi:10.1186/1471-230x-9-6 · Cited by 135 · see citing works
Self-citation
Friends with social benefits: host-microbe interactions as a driver of brain evolution and development?
Stilling, R. M., Bordenstein, S. R., Dinan, T. G., & Cryan, J. F. (2014) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2014.00147 · Cited by 135 · see citing works
Self-citation
Acute Tryptophan Depletion. Part I: Rationale and Methodology
Hood, S. D., Bell, C. J., & Nutt, D. J. (2005) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/j.1440-1614.2005.01627.x · Cited by 135 · see citing works
Regional Mucosa-Associated Microbiota Determine Physiological Expression of TLR2 and TLR4 in Murine Colon
Wang, Y., Devkota, S., Musch, M. W., Jabrì, B., Nagler‐Anderson, C., Antonopoulos, D. A., Chervonsky, A. V., & Chang, E. B. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013607 · Cited by 129 · see citing works
Mechanism of acute tryptophan depletion: is it only serotonin?
van Donkelaar, E. L., Blokland, A., Ferrington, L., Kelly, P. A. T., Steinbusch, H. W. M., & Prickaerts, J. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.9 · Cited by 127 · see citing works
L-Kynurenine/Aryl Hydrocarbon Receptor Pathway Mediates Brain Damage After Experimental Stroke
Cuartero, M., Ballesteros, I., de la Parra, J., Harkin, A., Abautret-Daly, Á., Sherwin, E., Fernández-Salguero, P., Corbí, Á., Lizasoaín, I., & Moro, M. A. (2014) · Circulation · doi:10.1161/circulationaha.114.011394 · Cited by 125 · see citing works
Tryptophan catabolism in females with irritable bowel syndrome: relationship to interferon‐gamma, severity of symptoms and psychiatric co‐morbidity
Fitzgerald, P., Eugene, M. C., Clarke, G. A., Scully, P., Barry, S., Eamonn, M. M. Q., Shanahan, F., Cryan, J. F., & Dinan, T. G. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01195.x · Cited by 122 · see citing works
Self-citation
A Distinct Profile of Tryptophan Metabolism along the Kynurenine Pathway Downstream of Toll-Like Receptor Activation in Irritable Bowel Syndrome
Clarke, G. A., McKernan, D. P., Gaszner, G., Quigley, E. M. M., Cryan, J. F., & Dinan, T. G. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00090 · Cited by 120 · see citing works
Self-citation
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
Indoleamine 2,3 dioxygenase in intestinal disease
Ciorba, M. A. (2012) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e32835c9cb3 · Cited by 116 · see citing works
The Aryl Hydrocarbon Receptor Meets Immunology: Friend or Foe? A Little of Both
Julliard, W. A., Fechner, J. H., & Mezrich, J. D. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00458 · Cited by 115 · see citing works
The microbiota link to irritable bowel syndrome
Jeffery, I. B., Quigley, E. M. M., Öhman, L., Simrén, M., & O’Toole, P. W. (2012) · Gut Microbes · doi:10.4161/gmic.21772 · Cited by 111 · see citing works
5-Hydroxytryptamine and human small intestinal motility: effect of inhibiting 5-hydroxytryptamine reuptake.
Gorard, S. A. C., Libby, G., & Farthing, M. J. G. (1994) · Gut · doi:10.1136/gut.35.4.496 · Cited by 107 · see citing works
Kynurenic Acid in the Digestive System–-New Facts, New Challenges
Turski, M. P., Turska, M., Paluszkiewicz, P., Parada-Turska, J., & Oxenkrug, G. F. (2013) · International Journal of Tryptophan Research · doi:10.4137/ijtr.s12536 · Cited by 106 · see citing works
Cognitive performance in irritable bowel syndrome: evidence of a stress-related impairment in visuospatial memory
Kennedy, P. J., Clarke, G., O‘Neill, A., Groeger, J. A., Quigley, E. M. M., Shanahan, F., Cryan, J. F., & Dinan, T. G. (2014) · Psychological Medicine · doi:10.1017/s0033291713002171 · Cited by 106 · see citing works
Self-citation
PRE- AND POSTNATAL EXPOSURE TO KYNURENINE CAUSES COGNITIVE DEFICITS IN ADULTHOOD
Pocivavsek, A., Wu, H., Elmer, G. I., Bruno, J. P., & Schwarcz, R. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08064.x · Cited by 105 · see citing works
Micromolar concentration of kynurenic acid in rat small intestine
Kuc, D., Zgrajka, W., Parada-Turska, J., Urbanik‐Sypniewska, T., & Turski, W. A. (2008) · Amino Acids · doi:10.1007/s00726-007-0631-z · Cited by 103 · see citing works
Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls
Kilkens, T. O. C., Honig, A., van Nieuwenhoven, M. A., Riedel, W. J., & Brummer, R. J. (2004) · Gut · doi:10.1136/gut.2004.041657 · Cited by 103 · see citing works
Astrocyte Indoleamine 2,3-Dioxygenase Is Induced by the TLR3 Ligand Poly(I:C): Mechanism of Induction and Role in Antiviral Response
Suh, H.-S., Zhao, M., Rivieccio, M. A., Choi, S., Connolly, E. C., Zhao, Y., Takikawa, O., Brosnan, C. F., & Lee, S. C. (2007) · Journal of Virology · doi:10.1128/jvi.00792-07 · Cited by 98 · see citing works
GR 38032F (Ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man
Talley, N., Phillips, S., Haddad, A., Miller, L., Twomey, C. K., Zinsmeister, A., Maccarty, R., & Ciociola, A. (1990) · Digestive Diseases and Sciences · doi:10.1007/bf01536922 · Cited by 95 · see citing works
Tryptophan synthase: a mine for enzymologists
Raboni, S., Bettati, S., & Mozzarelli, A. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0028-0 · Cited by 94 · see citing works
Kynurenic acid inhibits colon cancer proliferation in vitro: effects on signaling pathways
Walczak, K., Turski, W. A., & Rajtar, G. (2014) · Amino Acids · doi:10.1007/s00726-014-1790-3 · Cited by 92 · see citing works
DEVELOPMENT OF IMMUNOLOGICAL CAPACITY UNDER GERMFREE AND CONVENTIONAL CONDITIONS
Tlaskalová‐Hogenová, H., Šterzl, J., Štëpánková, R., Dlabač, V., Větvička, V., Rossmann, P., Mandel, L., & Rejnek, J. (1983) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1983.tb26862.x · Cited by 91 · see citing works
Evaluation of kynurenine pathway metabolism in Toxoplasma gondii-infected mice: Implications for schizophrenia
Notarangelo, F. M., Wilson, E. H., Horning, K. J., Thomas, M. A. R., Harris, T. H., Fang, Q., Hunter, C. A., & Schwarcz, R. M. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2013.11.011 · Cited by 91 · see citing works
A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor
Kawasaki, H., Chang, H., Tseng, H., Hsu, S.-C., Yang, S.-J., Hung, C.-H., Zhou, Y., & Huang, S.-K. (2014) · Allergy. European Journal of Allergy and Clinical Immunology · doi:10.1111/all.12346 · Cited by 90 · see citing works
Elevated levels of kynurenic acid during gestation produce neurochemical, morphological, and cognitive deficits in adulthood: Implications for schizophrenia
Pershing, M. L., Bortz, D. M., Pocivavsek, A., Fredericks, P. J., Jørgensen, C. V., Vunck, S. A., Leuner, B., Schwarcz, R. M., & Bruno, J. P. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.10.017 · Cited by 90 · see citing works
Serotonergic modulation of visceral sensation: lower gut
Camilleri, M. (2002) · Gut · doi:10.1136/gut.51.suppl_1.i81 · Cited by 90 · see citing works
Early developmental elevations of brain kynurenic acid impair cognitive flexibility in adults: Reversal with galantamine
Alexander, K., Pocivavsek, A., Wu, H., Pershing, M. L., Schwarcz, R. M., & Bruno, J. P. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.01.063 · Cited by 85 · see citing works
Basic Pathophysiologic Mechanisms in Irritable Bowel Syndrome
Mayer, E. A., Naliboff, B. D., & Chang, L. (2001) · Digestive Diseases · doi:10.1159/000050682 · Cited by 81 · see citing works
Toll-Like Receptor 4 Regulates Chronic Stress-Induced Visceral Pain in Mice
Tramullas, M., Finger, B. C., Moloney, R. D., Golubeva, A. V., Moloney, G., Dinan, T. G., & Cryan, J. F. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.11.004 · Cited by 81 · see citing works
Self-citation
Immunological Relevance of the Coevolution of IDO1 and AHR
Jaronen, M., & Quintana, F. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00521 · Cited by 80 · see citing works
Purine, Kynurenine, Neopterin and Lipid Peroxidation Levels in Inflammatory Bowel Disease
Forrest, C. M., Youd, P. L., Kennedy, A., Gould, S. R., Darlington, L. G., & Stone, T. W. (2002) · Journal of Biomedical Science · doi:10.1007/bf02256538 · Cited by 77 · see citing works
The microbiota and the gut-brain axis: insights from the temporal and spatial mucosal alterations during colonisation of the germfree mouse intestine
Aidy, S. E., Kunze, W., Bienenstock, J., & Kleerebezem, M. (2012) · Beneficial Microbes · doi:10.3920/bm2012.0042 · Cited by 72 · see citing works
Lack of host gut microbiota alters immune responses and intestinal granuloma formation during schistosomiasis
Holzscheiter, M., Layland, L. E., Loffredo‐Verde, E., Mair, K., Vogelmann, R., Langer, R., Wagner, H., & da Costa, C. P. (2013) · Clinical & Experimental Immunology · doi:10.1111/cei.12230 · Cited by 70 · see citing works
Levels of Purine, Kynurenine and Lipid Peroxidation Products in Patients with Inflammatory Bowel Disease
Forrest, C. M., Gould, S. R., Darlington, L. G., & Stone, T. W. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-0135-0_46 · Cited by 69 · see citing works
Shikimic Acid Production in Escherichia coli: From Classical Metabolic Engineering Strategies to Omics Applied to Improve Its Production
Martínez, J. A., Bolívar, F., & Escalante, A. (2015) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2015.00145 · Cited by 68 · see citing works
Human Indoleamine 2,3-Dioxygenase Is a Catalyst of Physiological Heme Peroxidase Reactions
Freewan, M., Rees, M. D., Plaza, T. S. S., Glaros, E. N., Lim, Y. J., Wang, X., Yeung, A. W. S., Witting, P. K., Terentis, A. C., & Thomas, S. R. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.410993 · Cited by 66 · see citing works
In vivo effects of the 5‐HT3 antagonist alosetron on basal and cholera toxin‐induced secretion in the human jejunum: a segmental perfusion study
Bearcroft, C. P., Andrè, E., & Farthing, M. J. G. (1997) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.1997.d01-1389.x · Cited by 66 · see citing works
Kynurenine aminotransferase and glutamine transaminase K of Escherichia coli: identity with aspartate aminotransferase
Han, Q., Fang, J., & Li, J. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3600617 · Cited by 63 · see citing works
Decreased levels of kynurenic acid in the intestinal mucosa of IBS patients: Relation to serotonin and psychological state
Keszthelyi, D., Troost, F. J., Jonkers, D. M. A. E., Kruimel, J. W., Leue, C., & Masclee, A. (2013) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2013.01.008 · Cited by 62 · see citing works

Flagged first, then by citations

Sorted by citations

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
Self-citation
Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease
Agus, A., Planchais, J., & Sokol, H. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.05.003 · Cited by 3,180 · see citing works
Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond
Platten, M., Nollen, E. A. A., Röhrig, U. F., Fallarino, F., & Opitz, C. A. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0016-5 · Cited by 1,586 · see citing works
Neurotransmitter modulation by the gut microbiota
Strandwitz, P. (2018) · Brain Research · doi:10.1016/j.brainres.2018.03.015 · Cited by 1,527 · 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 microbiota-gut-brain axis: from motility to mood
Margolis, K. G., Cryan, J. F., & Mayer, E. A. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.10.066 · Cited by 999 · see citing works
Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice
Burokas, A., Arboleya, S., Moloney, R. D., Peterson, V. L., Murphy, K., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.12.031 · Cited by 952 · see citing works
Self-citation
The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology
Rutsch, A., Kantsjö, J. B., & Ronchi, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.604179 · Cited by 821 · see citing works
The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications
Osadchiy, V., Martin, C. R., & Mayer, E. A. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.10.002 · Cited by 555 · 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
Feeding the microbiota–gut–brain axis: Diet, microbiome, and neuropsychiatry
Sandhu, K. V., Sherwin, E., Schellekens, H., Stanton, C., Dinan, T. G., & Cryan, J. F. (2017) · Translational Research · doi:10.1016/j.trsl.2016.10.002 · Cited by 491 · see citing works
Self-citation
Microbiota-derived metabolites as drivers of gut–brain communication
Ahmed, H., Leyrolle, Q., Koistinen, V., Kärkkäinen, O., Layé, S., Delzenne, N., & Hanhineva, K. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2102878 · Cited by 462 · see citing works
Gut Microbiota: An Integral Moderator in Health and Disease
Feng, Q., Chen, W.-D., & Wang, Y.-D. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00151 · Cited by 407 · see citing works
Microbiota-Gut-Brain Axis: New Therapeutic Opportunities
Long-Smith, C., O'Riordan, K. J., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2020) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023628 · Cited by 419 · 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
Relationship between the gut microbiome and brain function
Mohajeri, M. H., La Fata, G., Steinert, R. E., & Weber, P. (2018) · Nutrition Reviews · doi:10.1093/nutrit/nuy009 · Cited by 376 · see citing works
NLRP3 inflammasome-driven pathways in depression: clinical and preclinical findings
Kaufmann, F. N., Costa, A. P., Ghisleni, G., Diaz, A. P., Rodrigues, A. L. S., Peluffo, H., & Kaster, M. P. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.03.002 · Cited by 370 · see citing works
Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism
Golubeva, A. V., Joyce, S. A., Moloney, G., Burokas, A., Sherwin, E., Arboleya, S., Flynn, I., Khochanskiy, D., Moya-Pérez, A., Peterson, V., et al. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.09.020 · Cited by 364 · see citing works
Self-citation
Gut reactions: Breaking down xenobiotic–microbiome interactions
Clarke, G., Sandhu, K. V., Griffin, B. T., Dinan, T. G., Cryan, J. F., & Hyland, N. P. (2019) · Pharmacological Reviews · doi:10.1124/pr.118.015768 · Cited by 319 · see citing works
Self-citation
Cross talk: the microbiota and neurodevelopmental disorders
Kelly, J. R., Minuto, C., Cryan, J. F., Clarke, G., & Dinan, T. G. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00490 · Cited by 271 · see citing works
Self-citation
Gut microbiota changes in the extreme decades of human life: a focus on centenarians
Santoro, A., Ostan, R., Candela, M., Biagi, E., Brigidi, P., Capri, M., & Franceschi, C. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2674-y · Cited by 250 · see citing works
Gut feelings: a randomised, triple-blind, placebo-controlled trial of probiotics for depressive symptoms
Chahwan, B., Kwan, S., Isik, A., van Hemert, S., Burke, C., & Roberts, L. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.04.097 · Cited by 256 · see citing works
Tryptophan metabolites along the microbiota-Gut-Brain axis: an interkingdom communication system influencing the gut in health and disease
Bosi, A., Banfi, D., Bistoletti, M., Giaroni, C., & Baj, A. (2020) · International Journal of Tryptophan Research · doi:10.1177/1178646920928984 · Cited by 221 · see citing works
Focus on the essentials: tryptophan metabolism and the microbiome-gut-brain axis
Gheorghe, C. E., Martin, J. A., Manriquez, F. V., Dinan, T. G., Cryan, J. F., & Clarke, G. (2019) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2019.08.004 · Cited by 212 · see citing works
Self-citation
Stress and the Brain-Gut Axis in Functional and Chronic-Inflammatory Gastrointestinal Diseases: A Transdisciplinary Challenge
Labanski, A., Langhorst, J., Engler, H., & Elsenbruch, S. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.104501 · Cited by 200 · see citing works
Crosstalk between the microbiota-gut-brain axis and depression
Du, Y., Gao, X.-R., Peng, L., & Ge, J.-F. (2020) · Heliyon · doi:10.1016/j.heliyon.2020.e04097 · Cited by 191 · see citing works
Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders
Horn, J., Mayer, D. E., Chen, S., & Mayer, E. A. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01922-0 · Cited by 193 · see citing works
Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications
Mithaiwala, M. N., Santana-Coelho, D., Porter, G. A., & O’Connor, J. C. (2021) · Cells · doi:10.3390/cells10061548 · Cited by 190 · see citing works
Psychological stress in inflammatory bowel disease: Psychoneuroimmunological insights into bidirectional gut–brain communications
Ge, L., Liu, S., Li, S., Yang, J., Hu, G., Xu, C., & Song, W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1016578 · Cited by 187 · see citing works
The role of gut microbiota in bone homeostasis
Behera, J., Ison, J., Tyagi, S. C., & Tyagi, N. (2020) · Bone · doi:10.1016/j.bone.2020.115317 · Cited by 162 · see citing works
Association between gut microbiota and bone health: Potential mechanisms and prospective
Chen, Y.-C., Greenbaum, J., Shen, H., & Deng, H.-W. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-00513 · Cited by 165 · see citing works
Role of microbiota and tryptophan metabolites in the remote effect of intestinal inﬂammation on brain and depression
Waclawiková, B., & El Aidy, S. (2018) · Pharmaceuticals · doi:10.3390/ph11030063 · Cited by 172 · see citing works
Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications
Checa-Ros, A., Jeréz-Calero, A., Molina-Carballo, A., Campoy, C., & Muñoz-Hoyos, A. (2021) · Nutrients · doi:10.3390/nu13010249 · Cited by 164 · see citing works
Gutted! Unraveling the Role of the Microbiome in Major Depressive Disorder
Bastiaanssen, T. F. S., Cussotto, S., Claesson, M. J., Clarke, G., Dinan, T. G., & Cryan, J. F. (2020) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000243 · Cited by 159 · see citing works
Self-citation
Dietary polyphenols: Regulate the advanced glycation end products-RAGE axis and the microbiota-gut-brain axis to prevent neurodegenerative diseases
Li, Y., Peng, Y., Shen, Y., Zhang, Y., Liu, L., & Yang, X. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2076064 · Cited by 156 · see citing works
Gut hormones in microbiota-gut-brain cross-talk
Sun, L.-J., Li, J.-N., & Nie, Y.-Z. (2020) · Chinese Medical Journal · doi:10.1097/cm9.0000000000000706 · Cited by 145 · see citing works
Gut Microbiome and Osteoporosis
Ding, K., Hua, F., & Ding, W. (2020) · Aging and disease · doi:10.14336/ad.2019.0523 · Cited by 134 · see citing works
Considering Sex as a Biological Variable in Basic and Clinical Studies: An Endocrine Society Scientific Statement
Bhargava, A., Arnold, A. P., Bangasser, D. A., Denton, K. M., Gupta, A., Hilliard Krause, L. M., Mayer, E. A., McCarthy, M., Miller, W. L., Raznahan, A., et al. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnaa034 · Cited by 130 · see citing works
Mining microbes for mental health: determining the role of microbial metabolic pathways in human brain health and disease
Spichak, S., Bastiaanssen, T. F. S., Berding, K., Vlckova, K., Clarke, G., Dinan, T. G., & Cryan, J. F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.02.044 · Cited by 127 · see citing works
Self-citation
Gut microbes in neurocognitive and mental health disorders
Halverson, T., & Alagiakrishnan, K. (2020) · Annals of Medicine · doi:10.1080/07853890.2020.1808239 · Cited by 125 · see citing works
Bidirectional gut-brain-microbiota axis as a potential link between inflammatory bowel disease and ischemic stroke
Zhao, L., Xiong, Q., Stary, C. M., Mahgoub, O. K., Ye, Y., Gu, L., Xiong, X., & Zhu, S. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1382-3 · Cited by 113 · see citing works
Gut microbiome and bone
Ibáñez, L., Rouleau, M., Wakkach, A., & Blin-Wakkach, C. (2019) · Joint Bone Spine · doi:10.1016/j.jbspin.2018.02.008 · Cited by 103 · see citing works
Beneficial actions of microbiota‐derived tryptophan metabolites
Galligan, J. J. (2018) · Neurogastroenterology & Motility · doi:10.1111/nmo.13283 · Cited by 99 · see citing works
Going with the grain: Fiber, cognition, and the microbiota-gut-brain-axis
Berding, K., Carbia, C., & Cryan, J. F. (2021) · Experimental Biology and Medicine · doi:10.1177/1535370221995785 · Cited by 100 · see citing works
Self-citation
A Distinct Brain-Gut-Microbiome Profile Exists for Females with Obesity and Food Addiction
Dong, T. S., Mayer, E. A., Osadchiy, V., Chang, C., Katzka, W., Lagishetty, V., Gonzalez, K., Kalani, A., Stains, J., Jacobs, J. P., et al. (2020) · Obesity · doi:10.1002/oby.22870 · Cited by 95 · see citing works
Total glycosides from stems of Cistanche tubulosa alleviate depression-like behaviors: bidirectional interaction of the phytochemicals and gut microbiota
Fan, L., Peng, Y., Wang, J., Ma, P., Zhao, L., & Li, X. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153471 · Cited by 82 · see citing works
Is the Impact of Starvation on the Gut Microbiota Specific or Unspecific to Anorexia Nervosa? A Narrative Review Based on a Systematic Literature Search
Mack, I., Penders, J., Cook, J., Dugmore, J., Mazurak, N., & Enck, P. (2018) · Current Neuropharmacology · doi:10.2174/1570159x16666180118101354 · Cited by 79 · see citing works
Microbial regulation of hippocampal miRNA expression: implications for transcription of kynurenine pathway enzymes
Moloney, G. M., O’Leary, O. F., Salvo-Romero, E., Desbonnet, L., Shanahan, F., Dinan, T. G., Clarke, G., & Cryan, J. F. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.07.026 · Cited by 68 · see citing works
Self-citation
Relationships between Brain Activity, Tryptophan-Related Gut Metabolites, and Autism Symptomatology
Aziz-Zadeh, L., Ringold, S. M., Jayashankar, A., Kilroy, E., Butera, C., Jacobs, J. P., Tanartkit, S., Mahurkar-Joshi, S., Bhatt, R. R., Dapretto, M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58459-1 · Cited by 51 · see citing works
Intestinal Permeability and Its Significance in Psychiatric Disorders—A Narrative Review and Future Perspectives
Wasiak, J., & Gawlik-Kotelnicka, O. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114459 · Cited by 47 · see citing works
The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders
Młynarska, E., Barszcz, E., Budny, E., Gajewska, A., Kopeć, K., Wasiak, J., Rysz, J., & Franczyk, B. (2025) · Nutrients · doi:10.3390/nu17071135 · Cited by 44 · see citing works
Gut-Brain Axis: Probiotic,Bacillus subtilis, Prevents Aggression via the Modification of the Central Serotonergic System
Cheng, H.-W., Jiang, S., & Hu, J. (2019) · Oral Health by Using Probiotic Products · doi:10.5772/intechopen.86775 · Cited by 17 · see citing works
Harnessing Dietary Tryptophan: Bridging the Gap Between Neurobiology and Psychiatry in Depression Management
Chehadi, A. C., Pereira de Lima, E., Detregiachi, C. R. P., Santos de Argollo Haber, R., Catharin, V. M. C. S., Fornari Laurindo, L., Engracia Valenti, V., Machado Galhardi, C., Tanaka, M., & Maria Barbalho, S. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27010465 · Cited by 8 · see citing works

Central kynurenine pathway shift with age in women
de Bie, J., Guest, J., Guillemin, G. J., & Grant, R. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13496 · Cited by 83 · see citing works
The role of kynurenine pathway metabolites in the development of frailty in older adults
Pykhtina, V. S. (2023) · Problems of Geroscience · doi:10.37586/2949-4745-1-2023-15-24 · Cited by 1 · see citing works
Stimulatory effect of repeated treatment with lipopolysaccharide on a key enzyme of the kynurenine pathway in both genders in rats
Csanova, A., & Ježová, D. (2016) · European Pharmaceutical Journal · doi:10.1515/afpuc-2016-0009 · Cited by 2 · see citing works
Influence of plasma cytokines on kynurenine and kynurenic acid in schizophrenia
Chiappelli, J., Notarangelo, F. M., Pocivavsek, A., Thomas, M. A. R., Rowland, L., Schwarcz, R., & Hong, L. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0038-4 · Cited by 46 · see citing works
The role of the kynurenine pathway and quinolinic acid in adolescent major depressive disorder
Öztürk, M., Sapmaz, Ş. Y., Kandemir, H., Taneli, F., & Aydemir, Ö. (2020) · International journal of clinical practice · doi:10.1111/ijcp.13739 · Cited by 46 · see citing works

Authors: Kennedy, P. J., Cryan, J. F., Dinan, T. G., & Clarke, G.
Affiliations: University College Cork (IE)
Corresponding author: Clarke, G.
ORCID: Kennedy, P.J.
Cryan, J.F.
Clarke, G.
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2017-01
Volume: 112
Issue: Pt B
Pages: 399-412
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/j.neuropharm.2016.07.002
OpenAlex: W2469798172
Cited by: 724
References: 226
Citations by year: 2026: 78 · 2025: 81 · 2024: 106 · 2023: 93 · 2022: 82 · 2021: 83 · 2020: 72 · 2019: 47 · 2018: 45 · 2017: 28 · 2016: 9
FWCI: 2.58
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-nd)
Funders: Brain and Behavior Research Foundation (20771)
National Alliance for Research on Schizophrenia and Depression
Seventh Framework Programme (613979, FFP7- KBBE/2013–2018)
Science Foundation Ireland (HRA-POR-2014-64, SFI/12/RC/2273)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords: kynurenine pathway, gut microbiota, microbiota-gut-brain axis, tryptophan metabolism, serotonin synthesis, neuroendocrine regulation, anxiety, depression, social behavior, cognition, visceral pain, neurogastroenterology, immune system, microbiota-targeted therapy
MeSH terms: Gastrointestinal Microbiome, Animals, Brain, Humans, Kynurenine, Gastrointestinal Tract, Metabolic Networks and Pathways

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

Kynurenine pathway metabolism and the microbiota-gut-brain axis

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks