Volume 14 Issue 2
Mar.  2023
Turn off MathJax
Article Contents
LU Jinnan, ZHAO Chunhua, MIN Han. Mechanism of Action of Kynurenic Acid in Irritable Bowel Syndrome[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(2): 353-358. doi: 10.12290/xhyxzz.2022-0424
Citation: LU Jinnan, ZHAO Chunhua, MIN Han. Mechanism of Action of Kynurenic Acid in Irritable Bowel Syndrome[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(2): 353-358. doi: 10.12290/xhyxzz.2022-0424

Mechanism of Action of Kynurenic Acid in Irritable Bowel Syndrome

doi: 10.12290/xhyxzz.2022-0424
Funds:

Suzhou Gusu Health Talents Scientific Research Project GSWS2021041

The Research Project of Gusu School of Nanjing Medical University GSKY20210401

The Scientific and Technological Program of Suzhou SYSD2020140

More Information
  • Corresponding author: MIN Han, E-mail: minhan1981@163.com
  • Received Date: 2022-08-03
  • Accepted Date: 2022-09-05
  • Publish Date: 2023-03-30
  • Irritable bowel syndrome (IBS) is a common digestive psychosomatic diseases, mainly manifested as recurrent abdominal pain and abnormal bowel movements. The intestinal dysfunction is often comorbidized with anxiety, depression and other emotional problems, resulting in increased intestinal burden and even a decrease in the quality of life. The etiology and pathogenesis of IBS are unclear, but it is currently believed that IBS involves abnormal gut-brain interaction caused by a combination of various factors, including visceral hypersensitivity, intestinal immune activation, intestinal infection, intestinal dysbacteriosis, and psychosocial stress. Recent studies have observed the disorders of gut microbiota-regulated kynurinaine metabolism in IBS patients, and found that the metabolite kynurenic acid (KA) has important correlations with inflammatory responses, pain stimuli and mood changes. KA may play a protective role in IBS such as anti-inflammatory and pain relief and thus has the potential to become a new approach for the diagnosis and treatment of IBS. In this work, studies related to KA and IBS are reviewed.
  • loading
  • [1] 中华医学会消化病学分会胃肠功能性疾病协作组, 中华医学会消化病学分会胃肠动力学组. 2020年中国肠易激综合征专家共识意见[J]. 中华消化杂志, 2020, 40: 803-818. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLYS202110007.htm
    [2] Yildiz A, Kizil E, Yildiz A. Quality of life and psychometric evaluation of patients diagnosed with irritable bowel syndrome: an observational cohort study[J]. Sao Paulo Med J, 2020, 138: 282-286. doi:  10.1590/1516-3180.2019.0527.r1.16042020
    [3] Ford AC, Sperber AD, Corsetti M, et al. Irritable bowel syndrome[J]. Lancet, 2020, 396: 1675-1688. doi:  10.1016/S0140-6736(20)31548-8
    [4] 黄丹, 梁列新, 方秀才, 等. 精神心理因素对腹泻型肠易激综合征患者生命质量的影响[J]. 中华消化杂志, 2015, 35: 599-605.
    [5] 叶华, 于丰彦, 黄绍刚, 等. 腹泻型肠易激综合征患者的内脏敏感性与色氨酸代谢通路的相关性研究[J]. 胃肠病学, 2016, 21: 719-723. https://www.cnki.com.cn/Article/CJFDTOTAL-WIEC201612006.htm
    [6] Li P, Zheng J, Bai Y, et al. Characterization of kynurenine pathway in patients with diarrhea-predominant irritable bowel syndrome[J]. Eur J Histochem, 2020, 64: 3132.
    [7] Bosi A, Banfi D, Bistoletti M, et al. Tryptophan metabolites along the microbiota-gut-brain axis: an interkingdom communication system influencing the gut in health and disease[J]. Int J Tryptophan Res, 2020, 13: 1178646920928984.
    [8] Kennedy PJ, Cryan JF, Dinan TG, et al. Kynurenine pathway metabolism and the microbiota-gut-brain axis[J]. Neuropharmacology, 2017, 112: 399-412. doi:  10.1016/j.neuropharm.2016.07.002
    [9] Mishima Y, Ishihara S. Enteric Microbiota-Mediated Serotonergic Signaling in Pathogenesis of Irritable Bowel Syndrome[J]. Int J Mol Sci, 2021, 22: 10235. doi:  10.3390/ijms221910235
    [10] Vasant DH, Paine PA, Black CJ, et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome[J]. Gut, 2021, 70: 1214-1240. doi:  10.1136/gutjnl-2021-324598
    [11] Ala M. Tryptophan metabolites modulate inflammatory bowel disease and colorectal cancer by affecting immune system[J]. Int Rev Immunol, 2022, 41: 326-345. doi:  10.1080/08830185.2021.1954638
    [12] Maëva M, Elodie B, Nathalie R, et al. AhR/IL-22 pathway as new target for the treatment of post-infectious irritable bowel syndrome symptoms[J]. Gut Microbes, 2022, 14: 2022997. doi:  10.1080/19490976.2021.2022997
    [13] Luo M, Zhuang X, Tian Z, et al. Alterations in short-chain fatty acids and serotonin in irritable bowel syndrome: a systematic review and meta-analysis[J]. BMC Gastroenterol, 2021, 21: 14. doi:  10.1186/s12876-020-01577-5
    [14] Clarke G, Fitzgerald P, Cryan JF, et al. Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2, 3-dioxygenase activation in a male cohort[J]. BMC gastroenterol, 2009, 9: 6. doi:  10.1186/1471-230X-9-6
    [15] Hestad K, Alexander J, Rootwelt H, et al. The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depres-sive and Neurodegenerative Diseases[J]. Biomolecules, 2022, 12: 998. doi:  10.3390/biom12070998
    [16] Chen LM, Bao CH, Wu Y, et al. Tryptophan-kynurenine metabolism: a link between the gut and brain for depression in inflammatory bowel disease[J]. J Neuroinflammation, 2021, 18: 135. doi:  10.1186/s12974-021-02175-2
    [17] Klem F, Wadhwa A, Prokop LJ, et al. Prevalence, risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: a systematic review and meta-analysis[J]. Gastroenterology, 2017, 152: 1042-1054. doi:  10.1053/j.gastro.2016.12.039
    [18] Barbara G, Barbaro MR, Fuschi D, et al. Inflammatory and microbiota-related regulation of the intestinal epithelial barrier[J]. Front Nutr, 2021, 8: 718356. doi:  10.3389/fnut.2021.718356
    [19] González-Castro AM, Martínez C, Salvo-Romero E, et al. Mucosal pathobiology and molecular signature of epithelial barrier dysfunction in the small intestine in irritable bowel syndrome[J]. J Gastroenterol Hepatol, 2017, 32: 53-63.
    [20] Gaffen SL, Jain R, Garg AV, et al. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing[J]. Nat Rev Immunol, 2014, 14: 585-600. doi:  10.1038/nri3707
    [21] Tiszlavicz Z, Németh B, Fülöp F, et al. Different inhibitory effects of kynurenic acid and a novel kynurenic acid analogue on tumour necrosis factor-α (TNF-α) production by mononuclear cells, HMGB1 production by monocytes and HNP1-3 secretion by neutrophils[J]. Naunyn Schmiedebergs Arch Pharmacol, 2011, 383: 447-455. doi:  10.1007/s00210-011-0605-2
    [22] Mándi Y, Endrész V, Mosolygó T, et al. The opposite effects of kynurenic acid and different kynurenic acid analogs on tumor necrosis factor-α (TNF-α) production and tumor necrosis factor-stimulated gene-6 (TSG-6) expression[J]. Front Immunol, 2019, 10: 1406. doi:  10.3389/fimmu.2019.01406
    [23] Kaszaki J, Palásthy Z, Erczes D, et al. Kynurenic acid inhibits intestinal hypermotility and xanthine oxidase activity during experimental colon obstruction in dogs[J]. Neurogastroenterol Motil, 2008, 20: 53-62.
    [24] Moroni F, Fossati S, Chiarugi A, et al. Kynurenic acid actions in brain and periphery[J]. Int congr ser, 2007, 1304: 305-313. doi:  10.1016/j.ics.2007.07.016
    [25] Kiank C, Zeden JP, Drude S, et al. Psychological stress-induced, IDO1-dependent tryptophan catabolism: implications on immunosuppression in mice and humans[J]. PLoS One, 2010, 5: e11825. doi:  10.1371/journal.pone.0011825
    [26] Ferreira FS, Schmitz F, Marques EP, et al. Intrastriatal quinolinic acid administration impairs redox homeostasis and induces inflammatory changes: prevention by kynurenic acid[J]. Neurotox Res, 2020, 38: 50-58. doi:  10.1007/s12640-020-00192-2
    [27] Guillemin GJ. Quinolinic acid, the inescapable neurotoxin[J]. FEBS J, 2012, 279: 1356-1365. doi:  10.1111/j.1742-4658.2012.08485.x
    [28] Filpa V, Moro E, Protasoni M, et al. Role of glutamatergic neurotransmission in the enteric nervous system and brain-gut axis in health and disease[J]. Neuropharmacology, 2016, 111: 14-33. doi:  10.1016/j.neuropharm.2016.08.024
    [29] McRoberts JA, Coutinho SV, Marvizón JC, et al. Role of peripheral N-methyl-D-aspartate (NMDA) receptors in visceral nociception in rats[J]. Gastroenterology, 2001, 120: 1737-1748. doi:  10.1053/gast.2001.24848
    [30] Majláth Z, Török N, Toldi J, et al. Memantine and kynurenic acid: current neuropharmacological aspects[J]. Curr Neuropharmacol, 2016, 14: 200-209. doi:  10.2174/1570159X14666151113123221
    [31] Ciapała K, Mika J, Rojewska E. The kynurenine pathway as a potential target for neuropathic pain therapy design: from basic research to clinical perspectives[J]. Int J Mol Sci, 2021, 22: 11055. doi:  10.3390/ijms222011055
    [32] Ghasemi M, Phillips C, Trillo L, et al. The role of NMDA receptors in the pathophysiology and treatment of mood disorders[J]. Neurosci Biobehav Rev, 2014, 47: 336-358. doi:  10.1016/j.neubiorev.2014.08.017
    [33] Cao B, Zhu J, Zuckerman H, et al. Pharmacological interventions targeting anhedonia in patients with major depressive disorder: a systematic review[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2019, 92: 109-117. doi:  10.1016/j.pnpbp.2019.01.002
    [34] Zanos P, Piantadosi SC, Wu HQ, et al. The prodrug 4-chlorokynurenine causes ketamine-like antidepressant effects, but not side effects, by NMDA/glycineB-site inhibition[J]. J Pharmacol Exp Ther, 2015, 355: 76-85. doi:  10.1124/jpet.115.225664
    [35] Tan HL, Chiu SL, Zhu Q, et al. GRIP1 regulates synaptic plasticity and learning and memory[J]. Proc Natl Acad Sci USA, 2020, 117: 25085-25091. doi:  10.1073/pnas.2014827117
    [36] Li Y, Cheng X, Liu X, et al. Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions[J]. Front Pharmacol, 2022, 13: 831181. doi:  10.3389/fphar.2022.831181
    [37] Rodiño-Janeiro BK, Vicario M, Alonso-Cotoner C, et al. A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies[J]. Adv Ther, 2018, 35: 289-310. doi:  10.1007/s12325-018-0673-5
    [38] Johnsen PH, Hilpüsch F, Cavanagh JP, et al. Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial[J]. Lancet Gastroenterol Hepatol, 2018, 3: 17-24. doi:  10.1016/S2468-1253(17)30338-2
    [39] Shariati A, Fallah F, Pormohammad A, et al. The possible role of bacteria, viruses, and parasites in initiation and exacerbation of irritable bowel syndrome[J]. J Cell Physiol, 2019, 234: 8550-8569. doi:  10.1002/jcp.27828
    [40] Duan R, Zhu S, Wang B, et al. Alterations of Gut Microbiota in Patients With Irritable Bowel Syndrome Based on 16S rRNA-Targeted Sequencing: A Systematic Review[J]. Clin Transl Gastroenterol, 2019, 10: e00012. doi:  10.14309/ctg.0000000000000012
    [41] Carabotti M, Scirocco A, Maselli MA, et al. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems[J]. Ann Gastroenterol, 2015, 28: 203-209.
    [42] Kelly JR, Borre Y, O'Brien C, et al. Transferring the blues: depression-associated gut microbiota induces neurobehavi-oural changes in the rat[J]. J Psychiatr Res, 2016, 82: 109-118. doi:  10.1016/j.jpsychires.2016.07.019
    [43] Marin IA, Goertz JE, Ren T, et al. Microbiota alteration is associated with the development of stress-induced despair behavior[J]. Sci Rep, 2017, 7: 43859. doi:  10.1038/srep43859
    [44] Valladares R, Bojilova L, Potts AH, et al. Lactobacillus johnsonii inhibits indoleamine 2, 3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats[J]. FASEB J, 2013, 27: 1711-1720. doi:  10.1096/fj.12-223339
    [45] Desbonnet L, Garrett L, Clarke G, et al. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat[J]. J Psychiatr Res, 2008, 43: 164-174. doi:  10.1016/j.jpsychires.2008.03.009
    [46] Rudzki L, Ostrowska L, Pawlak D, et al. Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study[J]. Psychoneuroendocrinology, 2019, 100: 213-222. doi:  10.1016/j.psyneuen.2018.10.010
    [47] Tomás MS, Claudia Otero M, Ocaña V, et al. Production of antimicrobial substances by lactic acid bacteria I: determination of hydrogen peroxide[J]. Methods Mol Biol, 2004, 268: 337-346.
    [48] Wang Y, Devkota S, Musch MW, et al. Regional mucosa-associated microbiota determine physiological expression of TLR2 and TLR4 in murine colon[J]. PLoS One, 2010, 5: e13607. doi:  10.1371/journal.pone.0013607
    [49] Orhan F, Bhat M, Sandberg K, et al. Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes[J]. Scand J Immunol, 2016, 84: 262-271. doi:  10.1111/sji.12479
    [50] Martin-Gallausiaux C, Larraufie P, Jarry A, et al. Butyrate produced by commensal bacteria down-regulates indolamine 2, 3-dioxygenase 1 (IDO-1) expression via a dual mechan-ism in human intestinal epithelial cells[J]. Front Immunol, 2018, 9: 2838. doi:  10.3389/fimmu.2018.02838
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)

    Article Metrics

    Article views (251) PDF downloads(36) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return