Abstract:The pathogenesis of ulcerative colitis (UC) is still unclear, but it is generally considered to be caused by immune disorders caused by environmental factors, microorganisms, and metabolic disorders in the background of genetic susceptibility. As an essential amino acid in mammals, tryptophan can regulate intestinal barrier function, mucosal immune cells, and gut microbiota through different metabolic pathways, thereby participating in the occurrence and development of UC. Therefore, regulating the metabolic pathways or metabolites of tryptophan may become a new strategy for the treatment of UC in the future. This article will review the research progress of tryptophan metabolism and mechanism of the action in ulcerative colitis, in order to provide new ideas and methods for its clinical diagnosis and treatment.
黄灿 毛堂友 孙中美 李军祥 张文基 王志斌. 溃疡性结肠炎中的色氨酸代谢及作用机制[J]. 中国医药导报, 2023, 20(6): 55-58.
HUANG Can MAO Tangyou SUN Zhongmei LI Junxiang ZHANG Wenji WANG Zhibin. Tryptophan metabolism and mechanism of action in ulcerative colitis. 中国医药导报, 2023, 20(6): 55-58.
[1] Haq S,Grondin JA,Khan WI. Tryptophan-derived serotonin-kynurenine balance in immune activation and intestinal inflammation [J]. FASEB J,2021,35(10):e21888.
[2] 张弛,严时佳,万国辉.色氨酸与肿瘤免疫[J].药学学报:1-22[2022-07-29].
[3] 胡明富,卢海巧,陈伟琴.溃疡性结肠炎患者血清IDO与机体免疫失衡、炎症因子水平相关性研究[J].浙江中西医结合杂志,2019,29(6):475-478.
[4] Banskota S,Ghia JE,Khan WI. Serotonin in the gut:blessing or a curse [J]. Biochimie,2019,161:56-64.
[5] 任天华,吕敏敏,安晓萌,等.溃疡性结肠炎患者结肠黏膜5-HT信号通路的变化特点[J].国际消化病杂志,2019, 39(3):222-227.
[6] Dong F,Hao F,Murray IA,et al. Intestinal microbiota-derived tryptophan metabolites are predictive of Ah receptor activity [J]. Gut Microbes,2020,12(1):1-24.
[7] 李素素,常艳,魏伟.色氨酸2,3-双加氧酶调控炎症免疫反应在疾病中的作用[J].生理科学进展,2021,52(1):72-76.
[8] 张秀敏,赵昌东,李雪,等.溃疡性结肠炎患者血清吲哚胺2,3-双加氧化酶水平及其与外周血CD4+的关系[J].临床荟萃,2021,36(8):696-698.
[9] Yu J,Wang S,Yuan H,et al. Expression of Th17/Treg Cells in Peripheral Blood and Related Cytokines of Patients with Ulcerative Colitis of Different Syndrome Types and Correlation with the Disease [J]. Evid Based Complement Alternat,2021:4600947.
[10] Zhang X,Liu X,Zhou W,et al. Blockade of IDO-Kynurenine-AhR Axis Ameliorated Colitis-Associated Colon Cancer via Inhibiting Immune Tolerance [J]. Cell Mol Gastroenterol Hepatol,2021,12(4):1179-1199.
[11] Zhang S,Fang J,Liu Z,et al. Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis [J]. Stem Cell Res Ther,2021,12(1):50.
[12] Gargaro M,Vacca C,Massari S,et al. Engagement of Nuclear Coactivator 7 by 3-Hydroxyanthranilic Acid Enhances Activation of Aryl Hydrocarbon Receptor in Immunoregulatory Dendritic Cells [J]. Front Immunol,2019, 10:1973.
[13] Kwiatkowska I,Hermanowicz JM,Przybyszewska-Podstawka A,et al. Not Only Immune Escape-The Confusing Role of the TRP Metabolic Pathway in Carcinogenesis [J]. Cancers (Basel),2021,13(11):2667.
[14] 蒋志滨,高洁,李文,等.痛泻要方对TNBS诱导的肝郁脾虚型溃疡性结肠炎大鼠血清TNF-α、5-HT及肝组织SCD1、5-HT_2受体mRNA表达的影响[J].中华中医药学刊,2020,38(3):57-59,263.
[15] Capurso L,Friedmann CA. Distribution of 5-OH tryptamine (serotonin) in ulcerative colitis [J]. Proc R Soc Med,1970, 63(Suppl1):20-21.
[16] Szabo A,Gogolak P,Koncz G,et al. Immunomodulatory capacity of the serotonin receptor 5-HT2B in a subset of human dendritic cells [J]. Sci Rep,2018,8(1):1765.
[17] Li N,Ghia JE,Wang H,et al. Serotonin activates dendritic cell function in the context of gut inflammation [J]. Am J Pathol,2011,178(2):662-671.
[18] Ghia JE,Li N,Wang H,et al. Serotonin has a key role in pathogenesis of experimental colitis [J]. Gastroenterology,2009,137(5):1649-1660.
[19] Nieto C,Rayo I,de Las Casas-Engel M,et al. Serotonin (5-HT) Shapes the Macrophage Gene Profile through the 5-HT2B-Dependent Activation of the Aryl Hydrocarbon Receptor [J]. J Immunol,2020,204(10):2808-2817.
[20] Capellino S,Claus M,Watzl C. Regulation of natural killer cell activity by glucocorticoids,serotonin,dopamine,and epinephrine [J]. Cell Mol Immunol,2020,17(7):705-711.
[21] 万敏婕.5-HT通过5-HT7R调控调节性B细胞在溃疡性结肠炎中的作用研究[D].长春:吉林大学,2021.
[22] Ito M,Komai K,Mise-Omata S,et al. Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery [J]. Nature,2019,565(7738):246-250.
[23] Shajib MS,Chauhan U,Adeeb S,et al. Characterization of Serotonin Signaling Components in Patients with Inflammatory Bowel Disease [J]. J Can Assoc Gastroenterol,2019,2(3):132-140.
[24] Kwon YH,Wang H,Denou E,et al. Modulation of Gut Microbiota Composition by Serotonin Signaling Influences Intestinal Immune Response and Susceptibility to Colitis [J]. Cell Mol Gastroenterol Hepatol,2019,7(4):709-728.
[25] Monteleone I,Rizzo A,Sarra M,et al. Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract [J]. Gastroenterology,2011,141(1):237-248.
[26] Vacher S,Castagnet P,Chemlali W,et al. High AHR expression in breast tumors correlates with expression of genes from several signaling pathways namely inflammation and endogenous tryptophan metabolism [J]. PLoS One,2018, 13(1):e0190619.
[27] Shen J,Yang L,You K,et al. Indole-3-Acetic Acid Alters Intestinal Microbiota and Alleviates Ankylosing Spondylitis in Mice [J]. Front Immunol,2022,13:762580.
[28] Li YY,Wang XJ,Su YL,et al. Baicalein ameliorates ulcerative colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s [J]. Acta Pharmacol Sin,2022, 43(6):1495-1507.
[29] Lamas B,Richard ML,Leducq V,et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands [J]. Nat Med,2016, 22(6):598-605.
[30] Renga G,Nunzi E,Pariano M,et al. Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite [J]. J Immunother Cancer,2022,10(3):e003725.
[31] 刘慧泽,吴本升,王包晟,等.黄葵敛疡汤通过抑制炎症小体NLRP3改善葡聚糖硫酸钠诱导的小鼠溃疡性结肠炎[J].中华中医药学刊,2022,40(2):146-151,279- 283.
[32] Khan AS,Langmann T. Indole-3-carbinol regulates microglia homeostasis and protects the retina from degeneration [J]. J Neuroinflammation,2020,17(1):327.
[33] Yan T,Luo Y,Xia Y,et al. St.John’s Wort alleviates dextran sodium sulfate-induced colitis through pregnane X receptor-dependent NF-κB antagonism [J]. FASEB J,2021,35(11):e21968.
[34] Xiao HW,Cui M,Li Y,et al. Gut microbiota-derived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein [J]. Microbiome,2020,8(1):69.
[35] Dvo■ák Z,Kopp F,Costello CM,et al. Targeting the pregnane X receptor using microbial metabolite mimicry [J]. EMBO Mol Med,2020,12(4):e11621.