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
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 1,348
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
Flagged first, then by citations
Cited by
Sorted by citations
Items 701–800 of 1,006
Murakami, Y., Imamura, Y., Kasahara, Y., Yoshida, C., Momono, Y., Fang, K., Sakai, D., Konishi, Y., & Nishiyama, T. (2023) · Cells · doi:10.3390/cells12071087 · Cited by 36
Binvignat, M., Emond, P., Mifsud, F., Miao, B., Courties, A., Lefèvre, A., Maheu, E., Crema, M. D., Klatzmann, D., Kloppenburg, M., et al. (2023) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2023.04.007 · Cited by 37
Self-citationDual-directional regulation of spinal cord injury and the gut microbiota
Cui, Y., Liu, J., Xiao, L., Liu, S., Chen, H., Wei, Z., Li, H., Yang, Y., Zheng, C., & Li, Z. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.380881 · Cited by 38
“…pathway of tryptophan metabolism is the kynurenine pathway; both quinolinic and kynurenic acid, which are downstream metabolites of tryptophan, are neuroactive metabolites that regulate n-methyl-d-aspartic acid N-methyl-D-aspartate to influence memory function in the brain (Agus et al., 2018).”
BackgroundGut microbiome in the first 1000 days and risk for childhood food allergy
Davis, E. C., Monaco, C. L., Insel, R. A., & Järvinen, K. M. (2024) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2024.03.010 · Cited by 39
Microbiota–gut–brain axis: Natural antidepressants molecular mechanism
Lu, Y., Yu, X., Wang, Z., Kong, L., Jiang, Z., Shang, R., Zhong, X., Lv, S., Zhang, G., Gao, H., et al. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.156012 · Cited by 40
Gut microbial metabolism in ferroptosis and colorectal cancer
Cui, W., Hao, M., Yang, X. P., Yin, C., & Chu, B. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2024.08.006 · Cited by 40
Luo, Z., Liu, Y., Wang, X., Fan, F., Yang, Z., & Luo, D. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116554 · Cited by 49
Critical Review of the Cross-Links Between Dietary Components, the Gut Microbiome, and Depression
Randeni, N., & Xu, B. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26020614 · Cited by 44
Wu, X., Wei, J., Wang, R., Liu, D., Yi, Y., Gong, M., Liu, X., Gong, Q., Li, H., & Gao, J.-M. (2025) · Advanced Science · doi:10.1002/advs.202412234 · Cited by 37
Qin, L., Fan, B., Zhou, Y., Zheng, J., Diao, R., Wang, F., & Liu, J. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107625 · Cited by 40
Chen, C., Xiao, Q., Wen, Z., Gong, F., Zhan, H., Liu, J., Li, H., & Jiao, Y. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107654 · Cited by 38
Microbiota-mediated mechanisms of mucosal immunity across the lifespan
Iliev, I. D., Blander, J. M., Collins, N., Guo, C., Longman, R., Sonnenberg, G. F., Zeng, M. Y., & Artis, D. (2025) · Nature Immunology · doi:10.1038/s41590-025-02281-w · Cited by 55
“The gut microbiota metabolizes tryptophan to various indole metabolites, including indole-3-propionic acid and indole lactic acid 127 , which affect intestinal inflammation through aryl hydrocarbon receptor signaling pathways 127 .”
Yan, S., Xie, Y., Xv, J., Wang, K., Wang, J., Cao, Y., Han, X., Chen, F., Zhou, L., Jiang, Y., et al. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.120910 · Cited by 37
Kurhaluk, N., Kołodziejska, R., Kamiński, P., & Ткаченко, Г. М. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262311706 · Cited by 43
Yue, B., Yu, Z., Lv, C., Geng, X., Wang, Z., & Dou, W. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i30.4378 · Cited by 38
Influence of immunomodulatory drugs on the gut microbiota
Cohen, I., Ruff, W. E., & Longbrake, E. E. (2021) · Translational research · doi:10.1016/j.trsl.2021.01.009 · Cited by 39
Ma, S., Yu, J., Fu, J., Pan, L., Yu, H., Han, P., Zhang, Z., Peng, R., Xu, H., & Wang, Y. (2021) · Molecules · doi:10.3390/molecules26051377 · Cited by 37
“(3) Tryptamine (TA), produced by the bacterial decarboxylase from Trp, is responsible for mental and physical stress [31], and its derivatives generated in gut microbiota, such as indole-3-acetic acid (IAA), indole-3-propionic acid (IPA), and indole-3-lactic acid (ILA), are signal molecules that regulate intestinal pe…”
BackgroundInfluentialQi, R., Zhang, Z., Wang, J., Qiu, X., Wang, Q., Yang, F., Huang, J., & Liu, Z. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.623673 · Cited by 37
“These compounds are known to suppress the inflammatory response in humans and animals (Agus et al., 2018; Liang et al., 2018).”
BackgroundLiu, X., Dun, M., Jian, T., Sun, Y., Wang, M., Zhang, G., & Ling, J. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1134429 · Cited by 39
“After dephosphorylation, FOXO is in an activated state, which leads to gluconeogenesis (Agus et al., 2018).”
BackgroundLi, Q., You, Y., Zeng, Y., Wang, X., Pan, Z., Pang, J., Chen, Q., Zhou, Y., Jin, Y., Yang, Y., et al. (2022) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqac170 · Cited by 36
Li, L. J., Du, Y., Wang, Y., He, N., Wang, B., & Zhang, T. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s372389 · Cited by 36
Engineered 5-HT producing gut probiotic improves gastrointestinal motility and behavior disorder
Li, B., Li, M., Luo, Y., Li, R., Li, W., & Liu, Z. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.1013952 · Cited by 39
“The role of 5-HT in human health and disease has been widely studied (Lesurtel et al., 2008; Manocha and Khan, 2012; Agus et al., 2018).”
BackgroundIntestinal Flora Derived Metabolites Affect the Occurrence and Development of Cardiovascular Disease
Wen, Y., Sun, Z., Xie, S., Hu, Z., Lan, Q., Sun, Y., Yuan, L., & Zhai, C. (2022) · Journal of Multidisciplinary Healthcare · doi:10.2147/jmdh.s367591 · Cited by 39
“This may stimulate gastrointestinal motility through neurons in the enteric nervous system.(80) The aryl hydrocarbon receptor (AHR) is a transcription factor activated by the ligand in the cytoplasm and involved in multiple cellular processes.”
BackgroundSeeking the Psilocybiome: Psychedelics meet the microbiota-gut-brain axis
Kelly, J. R., Clarke, G. A., Harkin, A., Corr, S. C., Galvin, S. D., Pradeep, V., Cryan, J. F., O’Keane, V., & Dinan, T. G. (2022) · International Journal of Clinical and Health Psychology · doi:10.1016/j.ijchp.2022.100349 · Cited by 40
Kouno, T., Zeng, S.-L., Wang, Y., Duan, Y., Lang, S., Gao, B., Hartmann, P., Cabré, N., Llorente, C., Galbert, C., et al. (2023) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.15048 · Cited by 36
Self-citationTryptophan intake, not always the more the better
Hu, D., Liu, J., Yu, W., Li, C., Huang, L., Mao, W., & Lu, Z. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1140054 · Cited by 38
“Dietary tryptophan and its metabolites appear to have a potential role in the treatment of these disease (8).”
BackgroundInfluentialHarnessing the potential of probiotics in the treatment of alcoholic liver disorders
Mishra, G., Singh, P. N. D., Molla, M., Yimer, Y. S., Dinda, S. C., Chandra, P., Singh, B. K., Dagnew, S. B., Assefa, A. N., & Ewunetie, A. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1212742 · Cited by 39
“Research has shown that AhR ligands (metabolites of tryptophan) modulate the gut microbiota through IL-22 production by intestinal T cells (Agus et al., 2018; Natividad et al., 2018; Hendrikx et al., 2019).”
BackgroundLi, W., Jia, Y., Gong, Z., Zhao, D., Yu, F. H. Z., Fu, Y., Jiang, C., & Kong, W. (2023) · npj Science of Food · doi:10.1038/s41538-023-00212-3 · Cited by 36
“For instance, in the gut, the three major tryptophan metabolism pathways producing indole, serotonin, and kynurenine derivatives are directly or indirectly affected by the microbiota 27 .”
Zhou, Q., Tao, X., Guo, F., Wu, Y. C., Deng, D., Lv, L., Dong, D., Shang, D., & Xiang, H. (2023) · BMC Medicine · doi:10.1186/s12916-023-02997-2 · Cited by 41
“…regarded as an essential substance in host physiology, and the three tryptophan metabolism pathways were regulated by gut microbiota, involving 5-hydroxytryptamine (5-HT) production, ligands of the aryl hydrocarbon receptor (AhR), and kynurenine-producing indoleamine 2,3-dioxyge-nase pathways [23].”
BackgroundZhu, M., Dagah, O. M. A., Silaa, B. B., & Lu, J. (2023) · Antioxidants · doi:10.3390/antiox12091680 · Cited by 40
“Tryptophan, an essential amino acid, serves as a precursor for multiple metabolites involved in NAFLD [181].”
Parolisi, S., Montanari, C., Borghi, E., Cazzorla, C., Zuvadelli, J., Tosi, M., Barone, R. M. E., Bensi, G., Bonfanti, C., Dionisi‐Vici, C., et al. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106952 · Cited by 36
Skin microbe-dependent TSLP-ILC2 priming axis in early life is co-opted in allergic inflammation
Cha, J., Kim, T., Bhae, E., Gwak, H., Ju, Y., Choe, Y. H., Jang, I.-H., Jung, Y., Moon, S., Kim, T. H., et al. (2024) · Cell Host & Microbe · doi:10.1016/j.chom.2023.12.006 · Cited by 36
Arabinoxylan Alleviates Obesity by Regulating Gut Microbiota and Bile Acid Metabolism
Lin, J., Liu, H., Sun, Y., Zou, J., Nie, Q., & Nie, S. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c06392 · Cited by 40
Yu, S., Yin, Z., Ling, M., Chen, Z., Zhang, Y., Pan, Y., Zhang, Y., Cai, X., Chen, Z., Hao, H., et al. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.156186 · Cited by 38
Gut Microbiota and Immune System Dynamics in Parkinson’s and Alzheimer’s Diseases
Kuštrimović, N. Z., Balkhi, S., Bilato, G., & Mortara, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212164 · Cited by 39
“Gut microbiota also influences brain function by modulating neurotransmitter synthesis, such as acetylcholine, serotonin, norepinephrine, dopamine, and glutamate [21–23].”
Role of Uremic Toxins in Vascular Inflammation Associated with Chronic Kidney Disease
Chermiti, R., Burtey, S., & Dou, L. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13237149 · Cited by 39
Mou, W., Deng, Z., Zhu, L., Jiang, A., Lin, A., Xu, L., Deng, G., Huang, H., Guo, Z., Zhu, B., et al. (2025) · Science Advances · doi:10.1126/sciadv.adu1727 · Cited by 36
“Notably, IDO1 has been identified as a crucial immunoregulatory enzyme connecting host metabolic pathways and microbial signals in previous studies ( 83, 84 ).”
Gut microbiota-mediated modulation of host amino acid availability and metabolism
Han, Z., Zhao, L., Hu, Q., Hung, I., Liu, C., Liu, S., Mei, X., Zeng, X., Bin, P., & Wang, J. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2552345 · Cited by 44
“77,78 AHR activation, induces the expression of enzymes like indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO), involved in tryptophan catabolism, creating a feedback loop that affects AA availability.”
Nazzari, S., Molteni, M., Valtorta, F., Comai, S., & Frigerio, A. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.06.015 · Cited by 38
Huang, Z., Schoones, T., Wells, J. M., Fogliano, V., & Capuano, E. (2021) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202100092 · Cited by 36
Gao, N., Dou, X., Yin, T., Yang, Y., Yan, D., Ma, Z., Bi, C., & Shan, A. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.1c05820 · Cited by 36
Zhang, Q., Xiao, H., Zhan, J.-T., Yuan, B., & Feng, Y. (2022) · Chinese Chemical Letters · doi:10.1016/j.cclet.2022.01.004 · Cited by 36
Koppe, L., & Soulage, C. O. (2022) · Kidney International · doi:10.1016/j.kint.2022.06.025 · Cited by 38
Zheng, Z., Wang, S., Wu, C., Cao, Y., Gu, Q., Zhu, Y., Zhang, W., & Hu, W. (2022) · Nutrients · doi:10.3390/nu14173467 · Cited by 35
“In consideration of tryptophan co-metabolized by gut microbiota and host [12], and tryptophan metabolic balance influencing microglial activity [21], changes in various tryptophan metabolites produced from different metabolic pathways were f cused at 7 da s and 28 days p st-TBI.”
BackgroundInfluentialDopamine is an aryl hydrocarbon receptor agonist
Park, H., Jin, U.-H., Karki, K., Jayaraman, A., Allred, C. D., Michelhaugh, S. K., Mittal, S., Chapkin, R. S., & Safe, S. H. (2020) · Biochemical Journal · doi:10.1042/bcj20200440 · Cited by 36
Gao, N., Yang, Y., Liu, S., Fang, C., Dou, X., Zhang, L., & Shan, A. (2022) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c05381 · Cited by 36
Chen, Q., Fan, J., Lin, L., & Zhao, M. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.125534 · Cited by 35
Zhong, Y., Xiao, Q., Huang, J., Yu, S., Chen, L., Wan, Q., Zhang, Z., Luo, L., Song, L., Zhao, H., et al. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c04811 · Cited by 40
Luo, K., Chen, G., Zhang, Y., Moon, J., Xing, J., Peters, B. A., Usyk, M., Wang, Z., Hu, G., Li, J., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-023-00961-1 · Cited by 38
The gut microbiota in thrombosis
Khuu, M. P., Paeslack, N., Dremova, O., Benakis, C., Kiouptsi, K., & Reinhardt, C. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-024-01070-6 · Cited by 36
“A substantial amount of tryptophan that is not absorbed by the host is metabolized by gut bacteria, such as Clostridium spp. and E. coli via the indole–pyruvate pathway, producing bioactive indoles with immunomodulatory properties 126 .”
Gu, X., Zhou, Y., Zhang, Y., Wang, L., Gao, W., Luo, K., Sun, B., Li, T., Wang, H., Si, N., et al. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01587-5 · Cited by 39
“Preclinical evidence underscores the significance of the Trp-5-HT pathway in addressing cognitive decline and neuropathological changes associated with AD [7, 59].”
BackgroundTherapeutic potential of Parabacteroides distasonis in gastrointestinal and hepatic disease
Duan, J., Li, Q., Cheng, Y., Zhu, W., Liu, H., & Li, F. (2024) · MedComm · doi:10.1002/mco2.70017 · Cited by 37
Tan, Q., Deng, S., & Xiong, L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26030968 · Cited by 42
“Tryptophan can produce various metabolites through direct or indirect action by the gut microbiota and then be transported by transport proteins to intestinal epithelial cells, reaching the liver via the enterohepatic circulation, influencing liver function and metabolism [16].”
Mu, X., Feng, L., Wang, Q., Li, H., Zhou, H., Yi, W., & Sun, Y. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103580 · Cited by 35
“In recent years, IPA has attracted researcher ’ s attention as a novel protective factor for intestinal and metabolic diseases [18,67,68].”
InfluentialLu, Y., Yuan, H., Liang, S., Li, D., Jiang, P., Wang, X., Zhang, K., & Liu, D. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1603658 · Cited by 41
“Trp metabolism by gut microbiota generates biologically active derivatives including indole, kynurenine (Kyn), and quinolinic acid, which act as key ligands for Aryl hydrocarbon receptor (AhR) — a ligand-dependent transcription factor critical for immune homeostasis (15, 16).”
Gut microbiota promotes immune tolerance at the maternal-fetal interface
Brown, J. A., Amir, M., Yu, S., Wong, D. S. H., Gu, J., Balaji, U., Parkhurst, C. N., Hong, S., Hart, L. R., Carrow, H. C., et al. (2025) · Cell · doi:10.1016/j.cell.2025.11.022 · Cited by 35
Lee, D. M., Ecton, K. E., Trikha, S. R. J., Wrigley, S. D., Thomas, K. N., Battson, M. L., Wei, Y., Johnson, S. A., Weir, T. L., & Gentile, C. L. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00375.2019 · Cited by 36
Jackson, M. I., Waldy, C., & Jewell, D. E. (2020) · PLoS ONE · doi:10.1371/journal.pone.0241037 · Cited by 43
“Gut microbial metabolites of tryptophan [23, 84, 85] have beneficial health effects on gut and systemic physiology [77].”
BackgroundZheng, Z., Wu, L. M., Han, Y., Chen, J., Zhu, S., Yao, Y., Wang, B., & Li, L. (2021) · Engineering · doi:10.1016/j.eng.2020.12.013 · Cited by 36
“In the feces of Abx-treated mice, Trp was decreased, as well as indole-3-lactic acid (ILA), indole-3-pyruvic acid (IPYA), and indole-3-acetic acid (IAA), which were the products involved in the indole pathway of the gut microbial Trp metabolism [12].”
BackgroundInfluentialChen, D., He, J., Li, J., Zou, Q., Si, J., Guo, Y., Yu, J., Li, C., Wang, F., Chan, T., et al. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.643449 · Cited by 36
Tan, B., Chen, J., Qin, S., Liao, C., Zhang, Y., Wang, D., Li, S., Zhang, Z., Zhang, P., & Xu, F. (2021) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.1c00110 · Cited by 35
Clark, J. S., Simpson, B. S., & Murphy, K. J. (2021) · British Journal Of Nutrition · doi:10.1017/s0007114521003251 · Cited by 34
“The majority of dietary tryptophan is fed into the kynurenine pathway, leading to the creation of various end products that are involved in a host of physiological responses including neurotransmission, and immune system and inflammatory regulation(102,103).”
BackgroundColonization resistance against multi-drug-resistant bacteria: a narrative review
Guern, R. L., Stabler, S., Gosset, P., Pichavant, M., Grandjean, T., Faure, E., Karaca, Y., Faure, K., Kipnis, É., & Dessein, R. (2021) · Journal of Hospital Infection · doi:10.1016/j.jhin.2021.09.001 · Cited by 38
Liu, D., Wang, J., Zeng, H., Zhou, F., Wen, B., Zhang, X.-N., Luo, Y. L., Wu, W., Huang, J., & Liu, Z. (2021) · Food & Function · doi:10.1039/d1fo02181h · Cited by 35
Li, G., Zheng, X., Zhu, Y., Long, Y., & Xia, X. (2022) · Environmental Microbiology · doi:10.1111/1462-2920.15934 · Cited by 34
Recent Trends of Microbiota-Based Microbial Metabolites Metabolism in Liver Disease
Ganesan, R., Jeong, J., Kim, D. J., & Suk, K. T. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.841281 · Cited by 38
“Paracolobactrum coliforme, Proteus vulgaris (116, 117).”
Immunomodulation by foods and microbes: Unravelling the molecular tango
Forde, B. M., Yao, L., Shaha, R., Murphy, S., Lunjani, N., & O’Mahony, L. (2022) · Allergy · doi:10.1111/all.15455 · Cited by 35
Role of indoleamine 2,3-dioxygenase in pathology of the gastrointestinal tract
Acović, A., Gazdic, M., Jovicic, N. U., Harrell, C. R., Fellabaum, C., Arsenijević, N., & Volarević, V. (2018) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756284818815334 · Cited by 35
The Aged Intestine: Performance and Rejuvenation
Wang, Q., Qi, Y., Shen, W., Xu, J., Wang, L., Chen, S., Hou, T., & Si, J. (2021) · Aging and Disease · doi:10.14336/ad.2021.0202 · Cited by 36
Hong, Z.-S., Xie, J., Wang, X., Dai, J., Mao, J.-Y., Bai, Y., Sheng, J., & Tian, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.924178 · Cited by 34
“It is well known that L-tryptophan is an aromatic amino acid and a biosynthetic precursor of microbial and host metabolites (69, 70).”
BackgroundWu, L., Ran, L., Wu, Y., Liang, M., Jing, Z., Ke, F., Wang, F., Yang, J., Lao, X., Liu, L., et al. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.864571 · Cited by 37
“Tryptophan as an essential aromatic amino acid plays important roles in the “microbiotagut-brain axis”, and its metabolism is under the direct or indirect control of the gut microbiota (Agus et al., 2018).”
BackgroundZhang, Z., Yu, Z., Wang, J., Yu, Y., Li, L., Sun, P., Fan, X., & Xu, Q. (2022) · Microbial Cell Factories · doi:10.1186/s12934-022-01920-3 · Cited by 35
“In mammals, oxygen and L-tryptophan (L-Trp) are used as substrates for the biosynthesis of 5-HTP catalyzed by tryptophan hydroxylase (TPH), with Fe2+ and tetrahydrobiopterin (BH4) as cofactors [13, 14] (Fig.”
MethodContext-Dependent Regulation of Type17 Immunity by Microbiota at the Intestinal Barrier
Akuzum, B., & Lee, J. (2022) · Immune Network · doi:10.4110/in.2022.22.e46 · Cited by 36
“Tryptophan (Trp) metabolites and aryl hydrocarbon receptor (AHR) ligands Trp is an essential amino acid degraded by gut microbes, intestinal epithelial, and immune cells across three main pathways: a) the kynurenine pathway in both IECs and immune cells, b) the serotonin (5-HT) pathway via Trp hydroxylase 1 (TPH1) in…”
BackgroundContribution of Circulating Host and Microbial Tryptophan Metabolites Toward Ah Receptor Activation
Morgan, E. W., Dong, F., Annalora, A. J., Murray, I. A., Wolfe, T. M., Erickson, R., Gowda, K., Amin, S., Petersen, K. S., Kris‐Etherton, P. M., et al. (2023) · International Journal of Tryptophan Research · doi:10.1177/11786469231182510 · Cited by 35
Sah, R. K., Nandan, A., Athira, K. V., Prashant, S. K., Sankaran, S., Jose, A., Venkidasamy, B., & Nile, S. H. (2023) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2023.103861 · Cited by 37
Deng, R., Yu, S., Ruan, X., Liu, H., Zong, G., Peng, C., Tao, R., Chen, W., Wang, A., Zhao, Y., et al. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01265-3 · Cited by 34
“…whether the changes in the microbiota composition induced by capsaicin were associated with the exacerbated GC progression, we performed literature reviews and found that the predominant growth of Firmicutes and Clostridiales was closely associated with the elevated peripheral 5-HT levels [35–37].”
BackgroundMontgomery, T. L., Peipert, D., & Krementsov, D. N. (2024) · Immunological Reviews · doi:10.1111/imr.13343 · Cited by 38
“Changes in metabolism of tryptophan have also been extensively studied in MS. 134 In total, 90% of tryptophan is metabolized along the kynurenine pathway using one of two rate-limiting enzymes, in-doleamine 2,3 dioxygenase (IDO) in the brain, gut, and liver, or tryptophan 2,3 dioxygenase (TDO) in…”
Tao, K., Yuan, Y., Xie, Q., & Dong, Z. (2024) · Behavioural Brain Research · doi:10.1016/j.bbr.2024.115111 · Cited by 39
Tan, Z., Yu, P., Zhu, H., Gao, J., Han, N., Yang, C., Shen, Z., Gao, C., & Yang, X. (2024) · Food Chemistry · doi:10.1016/j.foodchem.2024.140934 · Cited by 34
Tiwari, S., & Paramanik, V. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04708-9 · Cited by 37
“The rate-limiting enzyme IDO1 mediates the metabolism of Trp via the KP in the gut, results in the synthesis of Kyn and subsequent products like niacin, quinolinic acid (QA), nicotinamide adenine dinucleotide, and kynurenic acid [43].”
Mechanisms of acupuncture in treating depression: a review
Ma, J., Yin, X., Cui, K., Wang, J., Li, W., & Xu, S. (2025) · Chinese Medicine · doi:10.1186/s13020-025-01080-7 · Cited by 34
“QA is an agonist of the NMDA receptor, which can mimic the effect of GLu and overac-tivate the NMDA receptor to cause nerve damage [88].”
Yang, C., Sun, J., Li, L., Zheng, J. H., Wang, C., Zhao, Y., Yun, D., Jia, M., Wu, Z., Liang, H., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70406 · Cited by 38
“24,29,57 Inthisstudy,thecorrelationbetweenthesebiosynthetic genes and ILA production in Lactobacillus was validated.”
Bretto, E., Caviglia, G. P., Saracco, G. M., Bugianesi, E., & Ribaldone, D. G. (2025) · Biomedicines · doi:10.3390/biomedicines13081807 · Cited by 41
“The SCD, initially developed in the 1920s for celiac disease, has been explored as a potential treatment for IBD due to its success in managing UC [124].”
Gut microbe-derived metabolites drive psoriatic inflammation via modulation of skin Th17 cells
Wang, C., Dai, S., Zhang, S., Zheng, Z., Zhou, Z., Chen, Z., Wang, M., Gao, Y., Yan, X., Xiong, W., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.08.006 · Cited by 38
Hu, Q., Tang, H., & Wang, Y. (2020) · Journal of Analysis and Testing · doi:10.1007/s41664-020-00126-z · Cited by 35
Chen, D., Wu, X., Chen, L., Hu, H.-H., Wang, Y., & Zhao, Y. (2020) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622320962648 · Cited by 34
“44,45 Tryptophan can also be transformed into indole-3-acetic acid that contributes to kidney dysfunction and increasesd the risk of cardiovascular events in CKD. 46,47 In contrast, a number of metabolites such as tryptanthrin play a renoprotective role.”
Manipulating effects of fruits and vegetables on gut microbiota – a critical review
Luo, J., Xian, L., Bordiga, M., Brennan, C. S., & Xu, B. (2020) · International Journal of Food Science & Technology · doi:10.1111/ijfs.14927 · Cited by 35
Gumpenberger, T., Brezina, S., Keski‐Rahkonen, P., Baierl, A., Robinot, N. R., Leeb, G., Habermann, N., Kok, D. E. G., Scalbert, A., Ueland, P. M., et al. (2021) · Metabolites · doi:10.3390/metabo11020119 · Cited by 32
“Those include several bacterial metabolites of tryptophan such as indole acetic acid, indole propionic acid, and indole lactic acid, which points towards a contribution of the gut microbiota in CRC development [35,36].”
BackgroundWu, L. M., Han, Y., Zheng, Z., Zhu, S., Chen, J., Yao, Y., Yue, S., Teufel, A., Weng, H., Li, L., et al. (2021) · Nutrients · doi:10.3390/nu13030940 · Cited by 36
“The indole derivatives were potential ligands of aryl hydrocarbon receptor (AhR) [14], which is a critical node in linking microbial tryptophan metabolites to brain function [63], and was involved in neuroinflammation [64].”
Backgroundvan den Bogaard, E. H. J., Esser, C., & Perdew, G. H. (2021) · Experimental Dermatology · doi:10.1111/exd.14409 · Cited by 35
Caffaratti, C., Plazy, C., Méry, G., Tidjani, A.-R., Fiorini, F., Thiroux, S., Toussaint, B., Hannani, D., & Gouëllec, A. L. (2021) · Metabolites · doi:10.3390/metabo11060406 · Cited by 36
Gut microbiota-related metabolome analysis based on chromatography-mass spectrometry
Zhou, L., Yu, D., Zheng, S., Ouyang, R., Wang, Y., & Xu, G. (2021) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2021.116375 · Cited by 35
Rannug, A. (2022) · Frontiers in Toxicology · doi:10.3389/ftox.2022.775010 · Cited by 35
“However, many common inhabitants of the intestinal biome metabolize the essential amino acid Trp, present at high levels in protein-rich food, into a variety of indoles (Agus et al., 2018; Gao et al., 2018).”
BackgroundLiu, W., Wang, Q., Chang, J., Bhetuwal, A., Bhattarai, N., & Ni, X. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.848508 · Cited by 33
“The effects of gut bacteria on the tryptophan metabolism in humans have been studied extensively (Agus et al., 2018).”
BackgroundInvestigating host-gut microbial relationship in Penaeus monodon upon exposure to Vibrio harveyi
Angthong, P., Uengwetwanit, T., Uawisetwathana, U., Koehorst, J. J., Arayamethakorn, S., Schaap, P. J., dos Santos, V. A. P. M., Phromson, M., Karoonuthaisiri, N., Chaiyapechara, S., et al. (2023) · Aquaculture · doi:10.1016/j.aquaculture.2023.739252 · Cited by 33
Zhou, X., Wu, X., Wu, Y. T., Yang, L., Shi, E., Ding, W., Chen, L., Shi, X., Feng, X., Su, C., et al. (2023) · Annals of Surgery · doi:10.1097/sla.0000000000005886 · Cited by 35
“Using the same cutoffs as the human metabolomics study, the top 3 molecules that were decreased in Amp group were IPA, trimethylamine N-oxide, and indole-3 sulfate, all of which are gut microbiota-derived molecules 32,38 (Fig.”
MethodCopper exposure causes alteration in the intestinal microbiota and metabolites in Takifugu rubripes
Liu, P., Liu, Y., Cheng, J., Xia, Y., & Yang, Y. T. (2024) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2024.116064 · Cited by 35
Fang, H., Hou, Q., Zhang, W., Su, Z., Zhang, J., Li, J., Lin, J., Wang, Z., Yu, X., Yang, Y., et al. (2024) · The Journal of Pain · doi:10.1016/j.jpain.2024.104535 · Cited by 33
Arto-Fernández, C., Rusu, E. C., Clavero-Mestres, H., Barrientos‐Riosalido, A., Bertran, L., Mahmoudian, R., Aguilar, C., Riesco, D., Chicote, J. U., Parada, D., et al. (2024) · European Journal of Clinical Investigation · doi:10.1111/eci.14279 · Cited by 38
Xie, X., Li, W., Xiong, Z., Xu, J., Liao, T., Sun, L., Xu, H., Zhang, M., Zhou, J., Xiong, W., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.09.014 · Cited by 35
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
