ТРИПТОФАН: КЛЮЧЕВОЙ МЕТАБОЛИТ ГОМЕОСТАЗА И РЕГУЛЯТОР ФУНКЦИЙ ОРГАНИЗМА
Аннотация
Введение. Триптофан – незаменимая аминокислота, которая содержится в основном в белковой пище и его доступность во многом зависит от рациона питания. Значительная часть триптофана метаболизируется в желудочно-кишечном тракте микробиотой кишечника, образуя ряд биологически активных молекул, включая лиганды арилуглеводородного рецептора, кинуренины, серотонин (5-гидрокситриптамин). Цель исследования. Провести анализ научных исследований, подтверждающих ключевую роль микробных катаболитов триптофана на функции макроорганизма. Материал и методы. Проведен анализ 47 англоязычных источников литературы, содержащих информацию об эффектах метаболитов триптофана на организм млекопитающих. Результаты. Установлено, что метаболизм триптофана играет центральную роль как в нормальном макроорганизме, так и при патологических состояниях, прямо или косвенно контролируется микробиотой кишечника. Выводы. Таким образом, метаболизм триптофана представляет собой важнейшую терапевтическую мишень, которая недостаточно используется для коррекции ряда хронических неврологических патологий и иммунокомпетентных состояний. Важный фактор – использование микроорганизмами нутрицевтиков и пробиотиков, модулирующих метаболизм триптофана в кишечнике и стимулирующих синтез специфических метаболитов.
Литература
Reilly JG, McTavish SF, Young AH. Rapid depletion of plasma tryptophan: A review of studies and experimental methodology. J Psychopharmacol. 1997;11:381-392. https://doi.org/10.1177/026988119701100416.
Mariotti F, Gardner CD. Dietary Protein and Amino Acids in Vegetarian Diets – A Review. Nutrients. 2019;11:2661. https://doi.org/10.3390/nu11112661.
Lesurtel M, Graf R, Aleil B, Walther DJ, Tian Y, Jochum W, Gachet C, Bader M, Clavien P-A. Platelet-derived serotonin mediates liver regeneration. Science. 2006;312:104-107. https://doi.org/10.1126/science.1123842.
Nyangale EP, Mottram DS, Gibson GR. Gut microbial activity, implications for health and disease: the potential role of metabolite analysis. J Proteome Res. 2012;11:5573-5585. https://doi.org/10.1021/pr300637d.
Evenepoel P, Claus D, Geypens B, Hiele M, Geboes K, Rutgeerts P, Ghooset Y. Amount and fate of egg protein escaping assimilation in the small intestine of humans. Am J Physiol. 1999;277(5):G935-943. https://doi.org/10.1152/ajpgi.1999.277.5.G935.
Watson MD, Cross BL, Grosicki GJ. Evidence for the Contribution of Gut Microbiota to Age-Related Anabolic Resistance. Nutrients. 2021;13(2):706-727. https://doi.org/10.3390/nu13020706.
Macfarlane GT, Cummings JH, Macfarlane S, Gibson GR. Influence of retention time on degradation of pancreatic enzymes by human colonic bacteria grown in a 3-stage continuous culture system. J Appl Bacteriol. 1989;67:520-527. https://doi.org/10.1111/j.1365-2672.1989.tb02524.x.
Krishnan S, Ding Y, Saedi N, Choi M, Sridharan GV, Sherr DH, Yarmush ML, Alaniz RC, Jayaraman A, Lee K. Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages. Cell Rep. 2018;23(4):1099-1111. https://doi.org/10.1016/j.celrep.2018.03.109.
Roager HM, Hansen LBS, Bahl MI, Frandsen HL, Carvalho V, Gøbel RJ, Dalgaard MD, Plichta DR, Sparholt MH, Vestergaard H, Hansen T, Sicheritz-Pontén T, Nielsen HB, Pedersen O, Lauritzen L, Kristensen M, Gupta R, Licht TR. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut. Nat Microbiol. 2016;1:16093. https://doi.org/10.1038/nmicrobiol.2016.93.
Pavlova T, Vidova V, Bienertova-Vasku J, Janku P, Almasi M, Klanova J, Spacil Z. Urinary intermediates of tryptophan as indicators of the gut microbial metabolism. Anal Chim Acta. 2017;987:72-80. https://doi.org/10.1016/j.aca.2017.08.022.
Dou L, Bertrand E, Cerini C, Faure V, Sampol J, Vanholder R, Berland Y, Brunet P. The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair. Kidney Int. 2004;65(2):442-451. https://doi.org/10.1111/j.1523-1755.2004.00399.x.
Geypens B, Claus D, Evenepoel P, Hiele M, Maes B, Peeters M, Rutgeerts P, Ghoos Y. Influence of dietary protein supplements on the formation of bacterial metabolites in the colon. Gut. 1997;41(1):70-76. https://doi.org/10.1136/gut.41.1.70.
Lee JH, Lee J. Indole as an intercellular signal in microbial communities. FEMS Microbiol Rev. 2010;34:426-444. https://doi.org/10.1111/j.1574-6976.2009.00204.x.
Dodd D, Spitzer MH, Van Treuren W, Merrill BD, Hryckowian AJ, Higginbottom SK, Le A, Cowan TM, Nolan GP, Fischbach MA, Sonnenburg JL. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature. 2017;551(7682):648-652. https://doi.org/10.1038/nature24661.
Wlodarska M, Luo C, Kolde R, d’Hennezel E, Annand JW, Heim CE, Krastel P, Schmitt EK, Omar AS, Creasey EA, Garner AL, Mohammadi S, O’Connell DJ, Abubucker S, Arthur TD, Franzosa EA, Huttenhower C, Murphy LO, Haiser HJ, Vlamakis H, Porter JA, Xavier RJ. Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation. Cell Host Microbe. 2017;22(1):25-37. https://doi.org/10.1016/j.chom.2017.06.007.
Cervantes-Barragan L, Chai JN, Tianero MD, Di Luccia B, Ahern PP, Merriman J, Cortez VS, Caparon MG, Donia MS, Gilfillan S, Cella M, Gordon JI, Hsieh C-S, Colonna M. Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells. Science. 2017;357(6353):806-810. https://doi.org/10.1126/science.aah5825.
Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, Haase S, Mähler A, Balogh A, Markó L, Vvedenskaya O, Kleiner FH, Tsvetkov D, Klug L, Costea PI, Sunagawa S, Maier L, Rakova N, Schatz V, Neubert P, Frätzer C, Krannich A, Gollasch M, Grohme DA, Côrte-Real BF, et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature. 2017;551:585-589. https://doi.org/10.1038/nature24628.
Smith EA, Macfarlane GT. Enumeration of human colonic bacteria producing phenolic and indolic compounds: effects of pH, carbohydrate availability and retention time on dissimilatory aromatic amino acid metabolism. J Appl Bacteriol. 1996;81(3):288-302. https://doi.org/10.1111/j.1365-2672.1996.tb04331.x.
Abildgaard A, Elfving B, Hokland M, Wegener G, Lund S. The microbial metabolite indole-3-propionic acid improves glucose metabolism in rats, but does not affect behaviour. Arch Physiol Biochem. 2018;124(4):306-312. https://doi.org/10.1080/13813455.2017.1398262.
Reimann F, Tolhurst G, Gribble FM. G-Protein-Coupled Receptors in Intestinal Chemosensation. Cell Metab. 2012;15(4):421-431. https://doi.org/10.1016/j.cmet.2011.12.019.
Koopman N, Katsavelis D, ten Hove AS, Brul S, de Jonge WJ, Seppen J. The Multifaceted Role of Serotonin in Intestinal Homeostasis. Int J Mol Sci. 2021;22(17):9487. https://doi.org/10.3390/ijms22179487.
Mawe GM, Hoffman JM. Serotonin signalling in the gutfunctions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol. 2013;10(10):473-486. https://doi.org/10.1038/nrgastro.2013.105.
Wandeputte D, Falony G, Vieira-Silva S, Tito RY, Joossens M, Raes J. Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut. 2016;65:57-62. https://doi.org/10.1136/gutjnl-2015-309618.
Chen H, Fink GR. Feedback control of morphogenesis in fungi by aromatic alcohols. Genes Dev. 2006;20(9):1150-1161. https://doi.org/10.1101/gad.1411806.
Elleuch L, Shaaban M, Smaoui S, Mellouli L, Karray-Rebai I, Fourati-Ben Fguira L, Shaaban KA, Laatsch H. Bioactive secondary metabolites from a new terrestrial Streptomyces sp. TN262. Appl Biochem Biotechnol. 2010;162(2):579-593. https://doi.org/10.1007/s12010-009-8808-4.
Jin M, Xu C, Zhang X. The effect of tryptophol on the bacteriophage infection in high-temperature environment. Appl Microbiol Biotechnol. 2015;99(19):8101-8111. https://doi.org/10.1007/s00253-015-6674-2.
Honoré AH, Aunsbjerg SD, Ebrahimi P, Thorsen M, Benfeldt C, Knøchel S, Skov T. Metabolic footprinting for investigation of antifungal properties of Lactobacillus paracasei. Anal Bioanal Chem. 2016;408(1):83-96. https://doi.org/10.1007/s00216-015-9103-6.
Narayanan TK, Rao GR. Beta-indoleethanol and beta-indolelactic acid production by Candida species: their antibacterial and autoantibiotic action. Antimicrob Agents Chemother. 1976;9(3):375-380. https://doi.org/10.1128/AAC.9.3.375.
Lee J-H, Kim Y-G, Kim M, Kim E, Choi H, Kim Y, Lee J. Indole-associated predator-prey interactions between the nematode Caenorhabditis elegans and bacteria. Environ Microbiol. 2017;19(5):1776-1790. https://doi.org/10.1111/1462-2920.13649.
Bommarius B, Anyanful A, Izrayelit Y, Bhatt S, Cartwright E, Wang W, Swimm AI, Benian GM, Schroeder FC, Kalman D. A family of indoles regulate virulence and Shiga toxin production in pathogenic E. coli. PLoS One. 2013;8(1):e54456. https://doi.org/10.1371/journal.pone.0054456.
Bansal T, Alaniz, RC, Wood TK, Jayaraman A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci. 2010;107(1):228-233. https://doi.org/10.1073/pnas.0906112107.
Shimada Y, Kinoshita M, Harada K, Mizutani M, Masahata K, Kayama H, Takeda K. Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon. PLoS One. 2013;8(11):600-604. https://doi.org/10.1371/journal.pone.0080604.
Venkatesh M, Mukherjee S, Wang H, Li H, Sun K, Benechet AP, Qiu Z, Maher L, Redinbo MR, Phillips RS, Fleet JC, Kortagere S, Mukherjee P, Fasano A, Le Ven J, Nicholson JK, Dumas ME, Khanna KM, Mani S. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity. 2014;41(2):296-310. https://doi.org/10.1016/j.immuni.2014.06.014.
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):e13178. https://doi.org/10.1111/nmo.13178.
Chimerel C, Emery E, Summers DK, Keyser U, Gribble FM, Reimann F. Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells. Cell Rep. 2014;9(4):1202-1208. https://doi.org/10.1016/j.celrep.2014.10.032.
Holst JJ. The Physiology of Glucagon-like Peptide 1. Physiol Rev. 2007;87(4):1409-1439. https://doi.org/10.1152/physrev.00034.2006.
Williams BB, Van Benschoten AH, Cimermancic P, Donia MS, Zimmermann M, Taketani M, Ishihara A, Kashyap PC, Fraser JS, Fischbach MA. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe. 2014;16(4):495-503. https://doi.org/10.1016/j.chom.2014.09.001.
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto J-M, Hansen T, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65. https://doi.org/10.1038/nature08821.
Sagheddu V, Patrone V, Miragoli F, Puglisi E, Morelli L. Infant Early Gut Colonization by Lachnospiraceae: High Frequency of Ruminococcus gnavus. Front Pediatr. 2016;4:57. https://doi.org/10.3389/fped.2016.00057.
Schirmer M, Smeekens SP, Vlamakis H, Jaeger M, Oosting M, Franzosa EA, Ter Horst R, Jansen T, Jacobs L, Bonder MJ, Kurilshikov A, Fu J, Joosten LAB, Zhernakova A, Huttenhower C, Wijmenga C, Netea MG, Xavier RJ. Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity. Cell. 2016;167(4):1125-1136.e8. https://doi.org/10.1016/j.cell.2016.10.020.
Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B, Ghiso J, Pappolla MA. Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole3-propionic acid. J Biol Chem. 1999;274(31):21937-21942. https://doi.org/10.1074/jbc.274.31.21937.
Kado S, Chang WLW, Chi AN, Wolny M, Shepherd DM, Vogel CFA. Aryl hydrocarbon receptor signaling modifies Toll-like receptor-regulated responses in human dendritic cells. Arch Toxicol. 2017;91(5):2209-2221. https://doi.org/10.1007/s00204-016-1880-y.
Banoglu E, Jha GG, King RS. Hepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate. Eur J Drug Metab Pharmacokinet. 2001;26(4):235-240. https://doi.org/10.1007/BF03226377.
Wu I-W, Hsu K-H, Lee C-C, Sun C-Y, Hsu H-J, Tsai C-J, Tzen C-Y, Wang Y-C, Lin C-Y, Wu M-S. p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. Nephrol Dial Transplant. 2011;26(3):938-947. https://doi.org/10.1093/ndt/gfq580.
Kim HY, Yoo T-H, Hwang Y, Lee GH, Kim B, Jang J, Yu HT, Kim MC, Cho J-Y, Lee CJ, Kim HC, Park S, Lee WW. Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD). Sci Rep. 2017;7(1):3057. https://doi.org/10.1038/s41598-017-03130-z.
Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci. 2009;106(10):3698-3703. https://doi.org/10.1073/pnas.0812874106.
Devlin AS, Marcobal A, Dodd D, Nayfach S, Plummer N, Meyer T, Pollard KS, Sonnenburg JL, Fischbach MA. Modulation of a Circulating Uremic Solute via Rational Genetic Manipulation of the Gut Microbiota. Cell Host Microbe. 2016;20(6):709-715. https://doi.org/10.1016/j.chom.2016.10.021.
