The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease
Open accessAbstract
The gut microbiota is a crucial actor in human physiology. Many of these effects are mediated by metabolites that are either produced by the microbes or derived from the transformation of environmental or host molecules. Among the array of metabolites at the interface between these microorganisms and the host is the essential aromatic amino acid tryptophan (Trp). In the gut, the three major Trp metabolism pathways leading to serotonin (5-hydroxytryptamine), kynurenine (Kyn), and indole derivatives are under the direct or indirect control of the microbiota. In this review, we gather the most recent advances concerning the central role of Trp metabolism in microbiota-host crosstalk in health and disease. Deciphering the complex equilibrium between these pathways will facilitate a better understanding of the pathogenesis of human diseases and open therapeutic opportunities.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The cited source says what the claim attributes to it.
In the citing paper
“In addition to the metabolic pathways leading to the production of 5-HT and kynurenine, microbial-derived indole derivatives of tryptophan are increasingly recognized as vital in the crosstalk between microbiota and host (Agus et al., 2018).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Agus et al., 2018
In the citing paper
“Thus, via influencing the amount of serotonin precursortryptophan, microbiota influence the amount of serotonin in the brain [32].”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [32]
In the citing paper
“Tryptophan metabolism across the serotonin, kynurenine and indole pathways, which are under control of the microbiota (Agus et al., 2018), has a strong influence on mucosal immunity and numerous systemic effects.”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Agus et al., 2018
In the citing paper
“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 [197]
In the citing paper
“Its synthesis by microbes has been well described (197).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [197]
In the citing paper
“Indoles are precursor molecules to many compounds that are critical for brain health and function and have been detected in the GI tract, brain, and the systemic circulation [32].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [32]
In the citing paper
“Of extreme relevance, the altered microbiota of patients could transfer the disease from a human host to a mouse host (113, 116–120).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [119]
In the citing paper
“The gut microbiota metabolizes dietary tryptophan into AhR agonists (119).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [119]
In the citing paper
“Tryptophan metabolism, specifically the main pathways leading to the production of 5-HT, kynurenine, and indole derivatives, appears to be closely regulated by the gut microbiota (378, 387).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [387]
In the citing paper
“Finally, the gut microbiota may influence 5-HT production by regulating tryptophan metabolism in the gut [ 69 ]. For example, the gut microbiota may upregulate the production of indole and kynurenine from tryptophan, thereby reducing the substrate for the production of 5-HT and consequently leading to FC.”
From Role of gut microbiota in functional constipation (2021) · cites this paper as [69]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D’Angelo, C., Massi-Benedetti, C., Fallarino, F., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.003 · Cited by 2,614
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
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
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 · cited 2×
“In this context, IDO1 activation in the periphery, notably in the case of inflammation, may remotely impact these cerebral processes, although the mechanisms involved remain unclear (Schwarcz et al., 2012).”
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
Self-citationA gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites
Dodd, D., Spitzer, M. H., Van Treuren, W., Merrill, B. D., Hryckowian, A. J., Higginbottom, S. K., Le, A., Cowan, T. M., Nolan, G. P., Fischbach, M. A., et al. (2017) · Nature · doi:10.1038/nature24661 · Cited by 1,425
Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health
Cervenka, I., Agudelo, L. Z., & Ruas, J. L. (2017) · Science · doi:10.1126/science.aaf9794 · Cited by 1,382
Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism
Gao, J., Xu, K., Liu, H., Liu, G., Bai, M., Peng, C., Li, T., & Yin, Y. (2018) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2018.00013 · Cited by 1,357
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
Cited by
Sorted by citations
Items 301–400 of 1,006
Yang, J., Liang, J., Hu, N., He, N., Liu, B., Liu, G., & Qin, Y. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70091 · Cited by 109
“Kyn can traverse the BBB to exert its effects within the brain [94].”
BackgroundBahman, F., Choudhry, K., Al‐Rashed, F., Al‐Mulla, F., Sindhu, S. T. A. K., & Ahmad, R. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1421346 · Cited by 106
Gut microbiota, kynurenine pathway and mental disorders – Review
Więdłocha, M., Marcinowicz, P., Janoska-Jaździk, M., & Szulc, A. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110145 · Cited by 90
Hsu, C., & Tain, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228705 · Cited by 86
“Tryptophan metabolism follows three major pathways in the gut: (1) the kynurenine pathway in both epithelial and immune cells; (2) the serotonin pathway in enterochromaffin cells; and (3) the indole pathway by the gut microbiota [14].”
BackgroundShi, J., Zhao, D., Song, S., Zhang, M., Zamaratskaia, G., Xu, X., Zhou, G., & Li, C. (2020) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.0c00245 · Cited by 85
Tarracchini, C., Milani, C., Longhi, G., Fontana, F., Mancabelli, L., Pintus, R., Lugli, G. A., Alessandri, G., Anzalone, R., Viappiani, A., et al. (2021) · Microbiology Spectrum · doi:10.1128/spectrum.01176-21 · Cited by 89
“The enzyme tryptophan 2,3-dioxygenase (TDO; EC 1.13.11.11), catalyzing the first and rate-limiting step of the KP, was detected with a 4-fold increase in healthy subjects (ANOVA P value of,0.05) (Table S7; Fig.”
BackgroundInfluentialBacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases
Stec, A., Sikora, M., Maciejewska, M., Paralusz-Stec, K., Michalska, M. N., Sikorska, E., & Rudnicka, L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043494 · Cited by 89
“The latter is known to be closely associated with microbiota metabolism [72].”
BackgroundZhang, X., Lau, H. C.-H., & Yu, J. Q. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2024.100018 · Cited by 100
Zhang, Z., Liu, H., Yu, B., Tao, H., Li, J., Wu, Z., Liu, G., Yuan, C., Guo, L., & Cui, B. (2020) · Food Research International · doi:10.1016/j.foodres.2020.109778 · Cited by 87
Microbiota-derived tryptophan metabolism: Impacts on health, aging, and disease
Gupta, S. K., Vyavahare, S. S., Blanes, I. L. D., Berger, F. G., Isales, C. M., & Fulzele, S. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112319 · Cited by 96
“Fang et al. (2022) reported that indole-3-carbaldehyde (I3C) produced by Bifidobacterium longum suppresses abnormal T helper type 2 immune response to improve atopic dermatitis symptoms in animal and clinical experiments through the AhR signaling pathway (Fang et al., 2022).”
BackgroundInfluentialThe microbiome: an integral player in immune homeostasis and inflammation in the respiratory tract
Perdijk, O., Azzoni, R., & Marsland, B. J. (2023) · Physiological Reviews · doi:10.1152/physrev.00020.2023 · Cited by 94
Rannug, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165681 · Cited by 83
“Abbreviations AHR aryl hydrocarbon receptor AHRE AHR response element AHRR AHR repressor ARNT nuclear translocator of AHR AMP antimicrobial peptides BUT butyrate CRC colorectal cancer DC dendritic cell DIM 3,3-Diindolylmethane DSS dextran sulfate sodium FICZ 6-Formylindolo[3,2-b]carbazole GF germ-free GPR109a G-protei…”
BackgroundInfluentialLin, H., Meng, L., Sun, Z., Shiming, S., Huang, X., Lin, N., Zhang, J., Lu, W., Yang, Q., Chi, J., et al. (2021) · Circulation Heart Failure · doi:10.1161/circheartfailure.120.008220 · Cited by 84
The Influence of Gut Microbiota on Neurogenesis: Evidence and Hopes
Sarubbo, F., Cavallucci, V., & Pani, G. (2022) · Cells · doi:10.3390/cells11030382 · Cited by 89
“(e) Chemical mediators from microbioma metabolism: communication between the gut microbiota and CNS also occurs through microbial-derived intermediates, the most relevant being SCFAs [33], tryptophan metabolites [73] and secondary bile acids [91].”
BackgroundMessengers From the Gut: Gut Microbiota-Derived Metabolites on Host Regulation
Li, C., Liang, Y., & Qiao, Y. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.863407 · Cited by 88
Dietary compounds in modulation of gut microbiota-derived metabolites
Feng, W., Liu, J., Cheng, H., Zhang, D., Tan, Y., & Peng, C. Y. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.939571 · Cited by 92
Liu, Y., Pei, Z., Pan, T., Wang, H., Chen, W., & Lu, W. (2023) · Microbiological Research · doi:10.1016/j.micres.2023.127392 · Cited by 88
Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease
Pandey, H., Jain, D., Tang, D. W. T., Wong, S. H., & Lal, D. (2023) · Intestinal Research · doi:10.5217/ir.2023.00080 · Cited by 95
Luo, Y., Fu, S., Liu, Y., Kong, S., Liao, Q., Lin, L., & Li, H. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.117990 · Cited by 88
Fan, L., Peng, Y., Wang, J., Ma, P., Zhao, L., & Li, X. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153471 · Cited by 82
The Gut Microbiome as a Regulator of the Neuroimmune Landscape
Yu, L. W., Agirman, G., & Hsiao, E. Y. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101320-014237 · Cited by 75
Baldi, S., Mundula, T., Nannini, G., & Amedei, A. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i39.6715 · Cited by 90
Guern, R. L., Grandjean, T., Stabler, S., Bauduin, M., Gosset, P., Kipnis, É., & Dessein, R. (2023) · Nature Communications · doi:10.1038/s41467-022-35767-4 · Cited by 85
Li, X., Shang, S., Wu, M., Song, Q., & Chen, D. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217096 · Cited by 87
Gut health: The results of microbial and mucosal immune interactions in pigs
Peng, J., Tang, Y., & Huang, Y. (2021) · Animal nutrition · doi:10.1016/j.aninu.2021.01.001 · Cited by 86
Gut microbiota: A new target of traditional Chinese medicine for insomnia
Feng, W., Yang, Z., Liu, Y., Chen, R., Song, Z., Pan, G., Zhang, Y., Guo, Z., Ding, X., Chen, L., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114344 · Cited by 88
Ma, L., Lyu, W., Song, Y., Chen, K., Lv, L., Yang, H., Wang, W., & Xiao, Y. (2023) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202200884 · Cited by 81
Oral magnesium prevents acetaminophen-induced acute liver injury by modulating microbial metabolism
Li, D., Chen, Y., Wan, M., Mei, F., Wang, F., Gu, P., Zhang, X., Wei, R., Zeng, Y., Zheng, H., et al. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.11.006 · Cited by 80
Zhang, B., Xu, Y., Liu, S., Lv, H., Hu, Y., Wang, Y., Li, Z., Wang, J., Ji, X., Ma, H., et al. (2020) · Nutrients · doi:10.3390/nu12082367 · Cited by 79
“Tryptophan is an essential amino acid for which humans rely on dietary supplementation, and can be converted into indole and indole derivatives by the gut microbiota [9].”
BackgroundTudela, H., Claus, S. P., & Saleh, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.719072 · Cited by 81
Gut microbiota: sculptors of the intestinal stem cell niche in health and inflammatory bowel disease
Markandey, M., Bajaj, A., Ilott, N. E., Kedia, S., Travis, S. P. L., Powrie, F. M., & Ahuja, V. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1990827 · Cited by 85
“Autologous organoid transplantation experiments and their success in restoration of healthy gut epithelium in mice models may unfurl newer avenues in regenerative medicine for targeting IBD.127,128 The therapeutic potential of the ISC transplantation relies heavily on our understanding of the ISC niche during health a…”
BackgroundInfluentialGut microbiota: A magical multifunctional target regulated by medicine food homology species
Zuo, W., Pang, Q., Yao, L.-P., Zhang, Y., Peng, C. Y., Huang, W., & Han, B. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.05.011 · Cited by 81
“Spearman correlation analysis showed that these bacteria were strongly correlated with a variety of liver metabolites, including caffeic acid [POS_13], erucic acid [POS_39], L-cystine [Neg_12], Ile-Ala [POS_8], etc. [73].”
Microbial Tryptophan Metabolism Tunes Host Immunity, Metabolism, and Extraintestinal Disorders
Liu, M., Nieuwdorp, M., de Vos, W. M., & Rampanelli, E. (2022) · Metabolites · doi:10.3390/metabo12090834 · Cited by 86
“Indeed, many microbial tryptophan derivatives— such as indole-3-acetic acid, indole-3-aldehyde, indole-3-acetaldehyde, indole-3-propionic acid, indole-3-lactic acid, indoleacrylic acid, tryptamine, 3-methylindole (skatole), and indoxyl sulfate—as well as bacteria- or host-derived kynurenine, are AhR agonists [58,69].”
BackgroundInfluentialCarotenoids Diet: Digestion, Gut Microbiota Modulation, and Inflammatory Diseases
Rocha, H. R., Coelho, M. C., Gomes, A., & Pintado, M. (2023) · Nutrients · doi:10.3390/nu15102265 · Cited by 90
Ma, Z., Akhtar, M. F., Pan, H., Liu, Q., Chen, Y., Zhou, X., You, Y., Shi, D., & Liu, H. (2023) · Microbiome · doi:10.1186/s40168-023-01569-z · Cited by 78
Shenhav, L., Fehr, K. B., Reyna, M. E., Petersen, C., Dai, D. L., Dai, R., Breton, V. L., Rossi, L., Smieja, M., Simons, E., et al. (2024) · Cell · doi:10.1016/j.cell.2024.07.022 · Cited by 92
Fontana, A., Manchia, M., Panebianco, C., Paribello, P., Arzedi, C., Cossu, E., Garzilli, M., Montis, M. A., Mura, A., Pisanu, C., et al. (2020) · Biomedicines · doi:10.3390/biomedicines8090311 · Cited by 78
Wang, J., Jia, R., Gong, H., Celi, P., Zhuo, Y., Ding, X., Bai, S., Zeng, Q., Yin, H., Xu, S., et al. (2021) · Antioxidants · doi:10.3390/antiox10091422 · Cited by 79
“Citation: Wang, J.; Jia, R.; Gong, H.; Celi, P.; Zhuo, Y.; Ding, X.; Bai, S.; Zeng, Q.; Yin, H.; Xu, S.; et al. The Effect of Oxidative Stress on the Chicken Ovary: Involvement of Microbiota and Melatonin Interventions.”
ResultInfluentialSun, P., Wang, M., Li, Z., Wei, J., Liu, F., Zheng, W., Zhu, X., Chai, X., & Zhao, S. (2022) · Theranostics · doi:10.7150/thno.72756 · Cited by 78
“Three major Trp metabolic pathways resulting in 5-hydroxytryptamine, Kyn, and indole derivatives are regulated by the gut microbiota [41].”
BackgroundInfluentialJing, W., Dong, S., Xu, Y., Liu, J., Ren, J., Liu, X., Zhu, M., Zhang, M., Shi, H., Li, N., et al. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.11.009 · Cited by 80
“Most of these metabolites exert their effects as signaling molecules and substrates for metabolic reactions to initiate an immune response within the gut mucosa and regulate inflamma-tory processes 4,9 .”
Effect of combined chronic predictable and unpredictable stress on depression-like symptoms in mice
Qiao, Y., Zhao, J., Li, C., Zhang, M., Wei, L., Zhang, X., Kurskaia, O. V., Bi, H., & Gao, T. (2020) · Annals of Translational Medicine · doi:10.21037/atm-20-5168 · Cited by 80
“the internal environment of the body (34), influencing the metabolic balance of the body, the activation of the immune system (35) and the HPA axis (36), as well as brain activity.”
BackgroundSerum metabolome and gut microbiome alterations in broiler chickens supplemented with lauric acid
Wu, Y., Zhang, H., Zhang, R., Cao, G., Li, Q., Zhang, B., Wang, Y., & Yang, C. (2021) · Poultry Science · doi:10.1016/j.psj.2021.101315 · Cited by 76
“It has been reported that beneficial intestinal microbes can secrete enzymes that are not encoded by the host genome to degrade polysaccharides, synthesize vitamins, and produce short-chain fatty acids (SCFAs) and tryptophan metabolites (Agus et al., 2018; Rowland et al., 2018).”
BackgroundNiu, L., Hou, Y., Jiang, M., & Bai, G. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114524 · Cited by 79
Xu, D., Wu, Q.-Y., Liu, W., Hu, G., Meng, H., & Wang, J. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.125919 · Cited by 79
Glycosidic linkages of fungus polysaccharides influence the anti-inflammatory activity in mice
Yuan, Q., Liu, W., Hao, W., Chen, Y., Xiao, Y., Li, H., Shui, M., Wu, D., & Wang, S. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.01.037 · Cited by 76
Inulin ameliorates schizophrenia via modulation of the gut microbiota and anti-inflammation in mice
Guo, L., Xiao, P., Zhang, X., Yang, Y., Yang, M., Wang, T., Lu, H., Tian, H., Wang, H., & Liu, J. (2021) · Food & Function · doi:10.1039/d0fo02778b · Cited by 74
Circadian Host-Microbiome Interactions in Immunity
Butler, T. D., & Gibbs, J. E. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01783 · Cited by 75
“Tryptophan Metabolites Tryptophan is a dietary essential amino acid metabolized in the gastrointestinal tract via three different pathways: the kynurenine pathway; the serotonin pathway; or via direct metabolism by microbiota (59).”
BackgroundSun, X., Zhao, D.-Y., Zhou, Y.-C., Wang, Q., Qin, G., & Yao, S. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i45.7173 · Cited by 75
Occurrence, impacts, and microbial transformation of 3-methylindole (skatole): A critical review
Ma, Q., Meng, N., Li, Y., & Wang, J. (2021) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2021.126181 · Cited by 76
Tryptophan metabolism and disposition in cancer biology and immunotherapy
Badawy, A. A. ‐. (2022) · Bioscience Reports · doi:10.1042/bsr20221682 · Cited by 80
Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress
Chen, Y., Tian, P., Wang, Z., Pan, R., Shang, K., Wang, G., Zhao, J., & Chen, W. (2022) · Nutrients · doi:10.3390/nu14235019 · Cited by 78
“Accumulating evidence has shown that the intestinal microbiota plays a vital role in ameliorating depression [5,6] and can influence critical physiological functions pertaining to immune system homeostasis, bacteria–host metabolism and even brain activity [7].”
BackgroundAre Microplastics Toxic? A Review from Eco-Toxicity to Effects on the Gut Microbiota
Niu, H., Liu, S., Jiang, Y., Hu, Y., Li, Y., He, L., Xing, M., Li, X., Wu, L., Chen, Z., et al. (2023) · Metabolites · doi:10.3390/metabo13060739 · Cited by 84
The tryptophan metabolic pathway of the microbiome and host cells in health and disease
Miyamoto, K., Sujino, T., & Kanai∥, T. (2024) · International Immunology · doi:10.1093/intimm/dxae035 · Cited by 85
“Most tryptophan metabolites are produced by both the host cells and bacteria (1, 38–40).”
Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice
Chajadine, M., Laurans, L., Radecke, T., Mouttoulingam, N., Al-Rifai, R., Bacquer, E., Delaroque, C., Rytter, H., Bredon, M., Knosp, C. A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50807-x · Cited by 79
“Trp is involved in various physiological processes and contributes to the maintenance of intestinal and systemic homeostasis in health and disease 3 – 5 .”
BackgroundSelf-citationDu, W., Jiang, S., Yin, S., Wang, R., Zhang, C., Yin, B., Li, J., Li, L., Qi, N., Zhou, Y. Q., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2400385121 · Cited by 80
“Three major pathways account for intestinal Trp metabolism and its role in the host–microbiota cross talk ( 9 ). i) The indole/aryl hydrocarbon receptor (AhR) pathway.”
MahmoudianDehkordi, S., Bhattacharyya, S., Brydges, C. R., Jia, W., Fiehn, O., Rush, A. J., Dunlop, B. W., & Kaddurah-Daouk, R. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.937906 · Cited by 75
“Certain gut bacteria regulate the production of neurotransmitters and their precursors, such as serotonin, gamma-aminobutyric acid and tryptophan, and they also regulate proteins such as brain-derived neurotrophic factor, a key molecule involved in neuroplastic changes in learning and memory (Bercik et al., 2010; O’Su…”
BackgroundLefèvre, A., Mavel, S., Nadal‐Desbarats, L., Galineau, L., Attucci, S., Dufour, D. F., Sokol, H., & Emond, P. (2018) · Talanta · doi:10.1016/j.talanta.2018.11.094 · Cited by 74
“Due to the multitude of physiological functions involving Trp metabolites, disruptions of its metabolism are associated with many pathologies such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), metabolic disorders (diabetes, obesity, non-alcoholic fatty liver disease, insulin resistance and ather…”
BackgroundSelf-citationManipulation of epithelial integrity and mucosal immunity by host and microbiota‐derived metabolites
Kayama, H., & Takeda, K. (2020) · European Journal of Immunology · doi:10.1002/eji.201948478 · Cited by 77
Cai, H., Wang, C., Qian, Y., Zhang, S., Zhang, C., Zhao, W., Zhang, T., Zhang, B., Chen, J., Liu, S., et al. (2021) · Human Brain Mapping · doi:10.1002/hbm.25419 · Cited by 74
Local and systemic effects of microbiome‐derived metabolites
Spivak, I., Fluhr, L., & Elinav, E. (2022) · EMBO Reports · doi:10.15252/embr.202255664 · Cited by 75
“Different end-products of microbial tryptophan metabolism can have either a beneficial or harmful impact (Agus et al , 2018; Paeslack et al , 2022).”
Mar, J. S., Ota, N., Pokorzynski, N. D., Peng, Y., Jaochico, A., Sangaraju, D., Skippington, E., Lekkerkerker, A., Rothenberg, M. E., Tan, M., et al. (2023) · Microbiome · doi:10.1186/s40168-023-01486-1 · Cited by 78
“5-HIAA, while predominately a product of host serotonin metabolism, can also be synthesized by select microbiota members [35, 36] (Fig.”
BackgroundGut Microbiota and its Metabolites: Bridge of Dietary Nutrients and Alzheimer’s Disease
Zhu, G., Zhao, J., Zhang, H., Wang, G., & Chen, W. (2023) · Advances in Nutrition · doi:10.1016/j.advnut.2023.04.005 · Cited by 78
“Tryptophan is metabolized by the microbiota through 3 major metabolic pathways: 2 predominant host pathways (serotonin [5hydroxytryptamine, 5-HT] and kynurenine) and 1 wellcharacterized microbial pathway (indole derivatives) [65].”
BackgroundLactobacillus reuteri in digestive system diseases: focus on clinical trials and mechanisms
Peng, Y., Ma, Y., Luo, Z., Jiang, Y.-F., Xu, Z., & Yu, R. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1254198 · Cited by 84
“The connection between the intestinal flora and the enteric neural systems involves the 5-HT pathways, which have advantages for irritating the local enteric nerve responses and promoting motility (Ge et al., 2017; Agus et al., 2018).”
BackgroundUnraveling the Role of the Human Gut Microbiome in Health and Diseases
Khalil, M., Ciaula, A. D., Mahdi, L., Jaber, N., Palo, D. M. D., Graziani, A., Baffy, G., & Portincasa, P. (2024) · Microorganisms · doi:10.3390/microorganisms12112333 · Cited by 100
Sehgal, R., de Mello, V. D., Männistö, V., Lindström, J., Tuomilehto, J. O., Pihlajamäki, J., & Uusitupa, M. I. J. (2022) · Nutrients · doi:10.3390/nu14214695 · Cited by 75
“It has been reported that IPA production in the gut is mainly regulated by tryptophan aminotransferase [23,26] and might also be dependent on bacterial tryptophanase [27].”
BackgroundMakizaki, Y., Uemoto, T., Yokota, H., Yamamoto, M., Tanaka, Y., & Ohno, H. (2021) · PLoS ONE · doi:10.1371/journal.pone.0248584 · Cited by 73
Martias, C., Baroukh, N., Mavel, S., Blasco, H., Lefèvre, A., Roch, L., Montigny, F., Gatien, J., Schibler, L., Dufour‐Rainfray, D., et al. (2021) · Molecules · doi:10.3390/molecules26144111 · Cited by 72
“The role of gut microbiota has been correlated with multiple gastrointestinal diseases, obesity [25], rheumatoid arthritis [26], psychiatric diseases such as autism [25] or depression [25], cardiovascular diseases, and type 2 diabetes [6].”
BackgroundTryptophan: From Diet to Cardiovascular Diseases
Melhem, N. J., & Taleb, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189904 · Cited by 75
“Among Trp catabolites, indoles play a pivotal role in human physiology, contributing to several functions, such as metabolic homeostasis, and immune system maturation and stimulation [33].”
BackgroundKouba, B. R., Camargo, A., Gil‐Mohapel, J., & Rodrigues, A. L. S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137077 · Cited by 77
“Within this scenario, it is worth noting that more than 90% of the body’s serotonin is produced in the gut, particularly by enterochromaffin cells, and alterations in the intestinal microbiota triggered by inflammatory processes have been shown to directly compromise the synthesis of this monoamine [32,33].”
The Role of the Human Microbiome in the Pathogenesis of Pain
Ustianowska, K., Ustianowski, Ł., Machaj, F., Gorący, A., Rosik, J., Szostak, B., Szostak, J., & Pawlik, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113267 · Cited by 77
Yang, W., Ren, D., Shao, H., Zhang, X., Li, T., Zhang, L., Liu, L., Zhao, Y., Niu, P., & Yang, X. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c06821 · Cited by 76
Pan, T., Pei, Z., Fang, Z., Wang, H., Zhu, J., Zhang, H., Zhao, J., Chen, W., & Lu, W. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1154346 · Cited by 74
“The catabolism of tryptophan in mammals mainly includes the kynurenine (KYN) pathway, the serotonin pathway, and the indole derivative pathway, of which the indole derivatives can only be produced by microbes (Agus et al., 2018).”
BackgroundXia, J., Guo, W., Hu, M., Jin, X., Zhang, S., Liu, B., Qiu, H., Wang, K., Zhuge, A., Li, S., et al. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2221450 · Cited by 75
“Indole and its derivatives are only produced by microbial catalysis and are known for their beneficial effects in suppressing inflammation, enhancing the gut barrier function, and ameliorating oxidative stress.(67) Several indole derivatives can attenuate hepatic lipogenesis and inflammatory infiltration in the pathog…”
BackgroundHu, B., Ye, C., Leung, E. L., Zhu, L., Hu, H., Zhang, Z., Zheng, J., & Liu, H. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104942 · Cited by 71
Intestinal Dysbiosis and Tryptophan Metabolism in Autoimmunity
Brown, J., Robusto, B. A., & Morel, L. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01741 · Cited by 68
“Therefore, the microbiota has an immense potential to produce Trp metabolites, including Kyn, which have the capacity to modulate the host immune system (51, 52).”
BackgroundShi, Z., Lei, H., Chen, G., Yuan, P., Cao, Z., Ser, H.-L., Zhu, X., Wu, F., Liu, C., Dong, M., et al. (2021) · mSystems · doi:10.1128/msystems.00985-20 · Cited by 71
“Indole, IAA, IPA, indole acrylic acid, and indole-3-aldehyde are commonly regarded as microbiota-derived AHR ligands (30).”
BackgroundChen, J., Wang, A., & Wang, Q. (2021) · BMC Bioinformatics · doi:10.1186/s12859-021-04199-0 · Cited by 73
Symbiont-regulated serotonin biosynthesis modulates tick feeding activity
Zhong, Z., Zhong, T., Peng, Y., Zhou, X., Wang, Z., Tang, H., & Wang, J. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2021.08.011 · Cited by 71
Molecular interactions between the intestinal microbiota and the host
Hertli, S., & Zimmermann, P. (2022) · Molecular Microbiology · doi:10.1111/mmi.14905 · Cited by 82
“AhR activation by indole promotes intestinal homeostasis, among other mechanisms, the increased production of IL- 22 (Table S1) (Agus et al., 2018; Alexeev et al., 2018; Lamas et al., 2018), which acts on intestinal epithelial cells, promoting proliferation and production of antimicrobial peptides…”
BackgroundWang, A., Guan, C., Wang, T., Mu, G., & Tuo, Y. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c06183 · Cited by 71
Ma, Y., Gou, S., Zhu, Z., Sun, J., Shahbazi, M., Si, T., Xu, C., Ru, J., Shi, X., Reis, R. L., et al. (2023) · Advanced Materials · doi:10.1002/adma.202309516 · Cited by 72
Wan, L., Qian, C., Yang, C., Peng, S., Dong, G., Cheng, P., Zong, G., Han, H., Shao, M., Gong, G., et al. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.130822 · Cited by 72
Burz, S. D., Monnoye, M., Philippe, C., Farin, W., Ratziu, V., Strozzi, F., Paillarse, J.-M., Chêne, L., Blottière, H. M., & Gérard, P. (2021) · Microorganisms · doi:10.3390/microorganisms9010199 · Cited by 75
Leschik, J., Lutz, B., & Gentile, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147339 · Cited by 77
Gut Microbiota in NSAID Enteropathy: New Insights From Inside
Wang, X., Tang, Q., Hou, H., Zhang, W., Li, M., Chen, D., Gu, Y., Wang, B., Hou, J., Liu, Y., et al. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.679396 · Cited by 75
Yang, M., Liu, J., Liu, C., Zhang, H., Li, S., Zhang, T., Yu, Z., Chi, X., Zhang, Z., & Du, Z. (2025) · ACS Nano · doi:10.1021/acsnano.4c11108 · Cited by 71
Neuroinflammation, Gut-Brain Axis and Depression
Evrensel, A., Ünsalver, B. Ö., & Ceylan, M. E. (2019) · Psychiatry Investigation · doi:10.30773/pi.2019.08.09 · Cited by 73
Role of tryptophan metabolism in cancers and therapeutic implications
Liu, X., & Zhai, X. (2021) · Biochimie · doi:10.1016/j.biochi.2021.01.005 · Cited by 73
Du, J., Zayed, A. A., Kigerl, K. A., Zane, K., Sullivan, M. B., & Popovich, P. G. (2021) · mSystems · doi:10.1128/msystems.01356-20 · Cited by 71
Yi, S., Dai, D., Wu, H., Chai, S., Liu, S., Meng, Q., & Zhou, Z. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.927206 · Cited by 68
“Although tryptophan is the least abundant amino acid in proteins and cells, it is a biosynthetic precursor for large number of microbial and host metabolites (32, 33).”
BackgroundSu, L., Zeng, Y., Li, G., Chen, J., & Chen, X. (2022) · Phytotherapy Research · doi:10.1002/ptr.7575 · Cited by 71
Liaqat, H., Parveen, A., & Kim, S. Y. (2022) · Nutrients · doi:10.3390/nu14163270 · Cited by 72
“The amino acid is metabolized via three different pathways in the gastrointes‐ tinal tract, namely, the direct metabolism of Trp, including ligands of the aryl hydrocar‐ bon receptor (AhR) [16] by gut microbiota; the kynurenine pathway in both immune and epithelial cells [17]; and the serotonin pathway (5‐hydroxytrypt…”
BackgroundInfluentialMetabolic reprogramming in colorectal cancer: regulatory networks and therapy
Zhang, J., Zou, S., & Fang, L. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-00977-w · Cited by 73
“The AhR pathway, which is important for sensing kynurenine metabolites to regulate CRC pathological progression, is processed by the gut microbiota [134].”
BackgroundWarner, D. R., Warner, J. B., Hardesty, J., Song, Y., King, T. N., Kang, J. X., Chen, C., Xie, S., Yuan, F., Prodhan, M. A. I., et al. (2019) · Journal of Lipid Research · doi:10.1194/jlr.ra119000200 · Cited by 65
“Tryptophan metabolism is a critical function of the gut microbiota that regulates many host functions, including metabolism and immunity (76).”
BackgroundTryptophan metabolites modify brain Aβ peptide degradation: A role in Alzheimer’s disease?
Maître, M., Klein, C., Patte‐Mensah, C., & Mensah‐Nyagan, A. G. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101800 · Cited by 69
Wang, J., Lin, H., Liu, Z., Zhang, W., Zhang, L., Jing, J., & Gao, A. (2022) · Chemosphere · doi:10.1016/j.chemosphere.2022.137499 · Cited by 67
Segers, A., & de Vos, W. M. (2023) · Microbiome Research Reports · doi:10.20517/mrr.2023.05 · Cited by 69
Li, Q., Formiga, R. D. O., Puchois, V., Creusot, L., Ahmad, A. H., Amouyal, S., Ribeiro, M. A. C., Zhao, Y., Harris, D. M. M., Lasserre, F., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01396-6 · Cited by 75
“IPA is known to be an AhR agonist 6 .”
Self-citationAnesi, A., Rubert, J., Oluwagbemigun, K., Orozco‐Ruiz, X., Nöthlings, U., Breteler, M. M. B., & Mattivi, F. (2019) · Metabolites · doi:10.3390/metabo9110261 · Cited by 71
Conley, J. M., Lambright, C. S., Evans, N., Medlock-Kakaley, E., Hill, D., McCord, J. P., Strynar, M. J., Wehmas, L. C., Hester, S., MacMillan, D. K., et al. (2021) · Environment International · doi:10.1016/j.envint.2021.107056 · Cited by 65
Metadata
- Authors
- Agus, A., Planchais, J., & Sokol, H.
- Affiliations
- AgroParisTech (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Sokol, Harry
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 23
- Issue
- 6
- Pages
- 716-724
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W2807728333
- Cited by
- 3,180
- References
- 60
- Citations by year
- 2026: 628 · 2025: 609 · 2024: 527 · 2023: 400 · 2022: 393 · 2021: 294 · 2020: 225 · 2019: 84 · 2018: 18
- FWCI
- 15.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Horizon 2020 Framework Programme (ANR-15-HDIM-0001-1, ERC-2016-StG-71577)
- European Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- gut microbiota, tryptophan metabolism, serotonin, kynurenine pathway, indole derivatives, microbial metabolites, aromatic amino acids, pathogenesis, therapeutic target
- MeSH terms
- Gastrointestinal Microbiome, Autistic Disorder, Colitis, Communicable Diseases, Crohn Disease, Humans, Indoles, Kynurenine, Obesity, Serotonin, Short Bowel Syndrome, Tryptophan, Inflammatory Bowel Diseases, Metabolic Syndrome, Gastrointestinal Tract
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
