Keywords
kynurenine
central nervous system
gut
gut microbiota
How to Cite
Abstract
The "brain–gut axis" is a bidirectional network of information exchange between the gut and the brain, in which tryptophan metabolism plays a central role, which is directly and indirectly regulated by the gut microbiota. Modulation of the gut microbiota composition is a promising therapeutic strategy for diseases associated with dysfunction of the "brain-gut axis". The aim of the study was to summarize the available literature data on the role of tryptophan metabolism in modulating the function of the "brain–gut axis". The current national and international scientific literature on the role of tryptophan metabolism in modulating the brain–gut axis was analyzed. To search for literature sources, the databases Scopus, PubMed, ResearchGate, Wiley Online Library, Google Scholar for 2018–2024 were studied, a total of 33 sources. The study described the mechanisms of serotonin and kynurenine synthesis. The impact of the gut microbiota on tryptophan metabolism in the gastrointestinal tract is considered. The role and place of serotonin, kynurenine and microbial tryptophan metabolites in the functioning of the "brain–gut axis" are described. We concluded that the gut microbiota modulates the function of the "brain–gut axis" through the interaction between the immune system, bacterial metabolites, and changes in tryptophan metabolism. Due to the fact that the composition of the gut microbiota of animals and humans is different, it is not possible to extrapolate the results of animal studies on the pathogenesis, pathophysiology and treatment of "brain–gut axis" disorders to the human population. There is a need for further human studies to explore the possibility of using tryptophan and its metabolites as biomarkers for diagnosis and development of new therapeutic strategies for diseases associated with "brain–gut axis" dysfunction. One of the options for such treatment may be methods of intestinal microbiota rebiosis that modulate tryptophan availability.
Keywords: serotonin, kynurenine, central nervous system, gut, gut microbiota.
References
Alzubide S, Alhalafi M. The Gut Brain Connection. Journal of Behavioral and Brain Science. 2024;14(3):103-17. DOI: 10.4236/jbbs.2024.143008.
Sliusar NA, Volosovets OP, Kryvopustov SP, Saltanova SD. The effect of neurotransmitters on the course of functional gastrointestinal disorders associated with emotional volitional disturbances caused by stress in children. Child’s Health. 2024;19(4):219-29. DOI: 10.22141/2224-0551.19.4.2024.1709. [In Ukrainian].
Grifka-Walk HM, Jenkins BR, Kominsky DJ. Amino Acid Trp: The Far Out Impacts of Host and Commensal Tryptophan Metabolism. Front Immunol. 2021;12:653208. DOI: 10.3389/fimmu.2021.653208. PMID: 34149693.
Margolis KG, Cryan JF, Mayer EA. The Microbiota-Gut-Brain Axis: From Motility to Mood. Gastroenterology. 2021;160(5):1486-501. DOI: 10.1053/j.gastro.2020.10.066. PMID: 33493503.
Hoglund E, Overli O, Winberg S. Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review. Front Endocrinol (Lausanne). 2019;10:158. DOI: 10.3389/fendo.2019.00158. PMID: 31024440.
Chojnacki C, Medrek-Socha M, Blonska A, Blasiak J, Poplawski T, Chojnacki J, Gasiorowska A. A Low FODMAP Diet Supplemented with L-Tryptophan Reduces the Symptoms of Functional Constipation in Elderly Patients. Nutrients. 2024;16(7):1027. DOI: 10.3390/nu16071027. PMID: 38613060.
Tsujita N, Akamatsu Y, Nishida MM, Hayashi T, Moritani T. Effect of Tryptophan, Vitamin B6, and Nicotinamide-Containing Supplement Loading between Meals on Mood and Autonomic Nervous System Activity in Young Adults with Subclinical Depression: A Randomized, Double-Blind, and Placebo-Controlled Study. J Nutr Sci Vitaminol (Tokyo). 2019;65(6):507-14. DOI: 10.3177/jnsv.65.507. PMID: 31902864.
Matis L, Daina LG, Maris L, Ghitea TC, Trifan DF, Moga I, Fodor R. Variety of Serotonin Levels in Pediatric Gastrointestinal Disorders. Diagnostics (Basel). 2023;13(24):3675. DOI: 10.3390/diagnostics13243675. PMID: 38132259.
Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Kynurenine pathway metabolism and the microbiota-gut-brain axis. Neuropharmacology. 2017;112:399-412. DOI: 10.1016/j.neuropharm.2016.07.002. PMID: 27392632.
Roth W, Zadeh K, Vekariya R, Ge Y, Mohamadzadeh M. Tryptophan Metabolism and Gut-Brain Homeostasis. Int J Mol Sci. 2021;22(6):2973. DOI: 10.3390/ijms22062973. PMID: 33804088.
Keating DJ, Spencer NJ. What is the role of endogenous gut serotonin in the control of gastrointestinal motility? Pharmacol Res. 2019;140:50-5. DOI: 10.1016/j.phrs.2018.06.017. PMID: 29935946.
Guzel T, Mirowska-Guzel D. The Role of Serotonin Neurotransmission in Gastrointestinal Tract and Pharmacotherapy. Molecules. 2022;27(5):1680. DOI: 10.3390/molecules27051680. PMID: 35268781.
Binda S, Tremblay A, Iqbal UH, Kassem O, Le Barz M, Thomas V, et al. Psychobiotics and the Microbiota-Gut-Brain Axis: Where Do We Go from Here? Microorganisms. 2024;12(4):634. DOI: 10.3390/microorganisms12040634. PMID: 38674579.
Martin-Gallausiaux C, Larraufie P, Jarry A, Beguet-Crespel F, Marinelli L, Ledue F, et al. Butyrate Produced by Commensal Bacteria Down-Regulates Indolamine 2,3-Dioxygenase 1 (IDO-1) Expression via a Dual Mechanism in Human Intestinal Epithelial Cells. Front Immunol. 2018;9:2838. DOI: 10.3389/fimmu.2018.02838. PMID: 30619249.
Laurans L, Venteclef N, Haddad Y, Chajadine M, Alzaid F, Metghalchi S, et al. Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health. Nat Med. 2018;24(8):1113-20. DOI: 10.1038/s41591-018-0060-4. PMID: 29942089.
Lashgari NA, Roudsari NM, Shayan M, Niazi Shahraki F, Hosseini Y, Momtaz S, Abdolghaffari AH. IDO/Kynurenine; novel insight for treatment of inflammatory diseases. Cytokine. 2023;166:156206. DOI: 10.1016/j.cyto.2023.156206. PMID: 37120946.
Su X, Gao Y, Yang R. Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis. Cells. 2022;11(15):2296. DOI: 10.3390/cells11152296. PMID: 35892593.
Beurel E. Stress in the microbiome-immune crosstalk. Gut Microbes. 2024;16(1):2327409. DOI: 10.1080/19490976.2024.2327409. PMID: 38488630.
Roager HM, Licht TR. Microbial tryptophan catabolites in health and disease. Nat Commun. 2018;9(1):3294. DOI: 10.1038/s41467-018-05470-4. PMID: 30120222.
Bhattarai Y, Williams BB, Battaglioli EJ, Whitaker WR, Till L, Grover M, et al. Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion. Cell Host Microbe. 2018;23(6):775-85.e5. DOI: 10.1016/j.chom.2018.05.004. PMID: 29902441.
Jaglin M, Rhimi M, Philippe C, Pons N, Bruneau A, Goustard B, et al. Indole, a Signaling Molecule Produced by the Gut Microbiota, Negatively Impacts Emotional Behaviors in Rats. Front Neurosci. 2018;12:216. DOI: 10.3389/fnins.2018.00216. PMID: 29686603.
Jennis M, Cavanaugh CR, Leo GC, Mabus JR, Lenhard J, Hornby PJ. Microbiota-derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo. Neurogastroenterol Motil. 2018;30(2). DOI: 10.1111/nmo.13178. PMID: 28782205.
Agus A, Planchais J, Sokol H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018;23(6):716-24. DOI: 10.1016/j.chom.2018.05.003. PMID: 29902437.
De Vadder F, Grasset E, Manneras Holm L, Karsenty G, Macpherson AJ, Olofsson LE, Backhed F. Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks. Proc Natl Acad Sci U S A. 2018;115(25):6458-63. DOI: 10.1073/pnas.1720017115. PMID: 29866843.
Fan L, Xia Y, Wang Y, Han D, Liu Y, Li J, et al. Gut microbiota bridges dietary nutrients and host immunity. Sci China Life Sci. 2023;66(11):2466-514. DOI: 10.1007/s11427-023-2346-1. PMID: 37286860.
Tripp P, Davis EC, Gurung M, Rosa F, Bode L, Fox R, et al. Infant Microbiota Communities and Human Milk Oligosaccharide Supplementation Independently and Synergistically Shape Metabolite Production and Immune Responses in Healthy Mice. J Nutr. 2024;154(9):2871-86. DOI: 10.1016/j.tjnut.2024.07.031. PMID: 39069270.
Orhan F, Bhat M, Sandberg K, Stahl S, Piehl F, Svensson C, et al. Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes. Scand J Immunol. 2016;84(5):262-71. DOI: 10.1111/sji.12479. PMID: 27607184.
Dubois T, Zdanowicz N, Jacques D, Lepiece B, Jassogne C. Microbiota Diversity and Inflammation as a New Target to Improve Mood: Probiotic Use in Depressive Disorder. Psychiatr Danub. 2023;35(2):72-6. PMID: 37800206.
Yang Z, Su H, Lv Y, Tao H, Jiang Y, Ni Z, et al. Inulin intervention attenuates hepatic steatosis in rats via modulating gut microbiota and maintaining intestinal barrier function. Food Res Int. 2023;163:112309. DOI: 10.1016/j.foodres.2022.112309. PMID: 36596207.
Sun M, Ma N, He T, Johnston LJ, Ma X. Tryptophan (Trp) modulates gut homeostasis via aryl hydrocarbon receptor (AhR). Crit Rev Food Sci Nutr. 2020;60(10):1760-8. DOI: 10.1080/10408398.2019.1598334. PMID: 30924357.
Montgomery TL, Eckstrom K, Lile KH, Caldwell S, Heney ER, Lahue KG, et al. Lactobacillus reuteri tryptophan metabolism promotes host susceptibility to CNS autoimmunity. Microbiome. 2022;10(1):198. DOI: 10.1186/s40168-022-01408-7. PMID: 36419205.
Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 2016;22(6):586-97. DOI: 10.1038/nm.4106. PMID: 27158906.
Juricek L, Coumoul X. The Aryl Hydrocarbon Receptor and the Nervous System. Int J Mol Sci. 2018;19(9):2504. DOI: 10.3390/ijms19092504. PMID: 30149528.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.