脑肠轴作为中枢神经系统疾病治疗靶点的研究进展
Research Progress of the Brain-Gut Axis as a Therapeutic Target for Central Nervous System Diseases
DOI: 10.12677/ACM.2023.133496, PDF,    国家自然科学基金支持
作者: 安 刚*：济宁医学院临床医学院，山东 济宁；宋慧敏, 崔昌萌#：济宁医学院附属医院神经外科监护室，山东 济宁
关键词: 脑肠轴；中枢神经系统疾病；诊断和治疗；Brain-Gut Axis； Central Nervous System Disease； Diagnosis and Treatment
摘要: 脑肠轴是由胃肠道与中枢神经系统之间双向的信息交流组成，在大脑情绪和认知中枢与外周肠道功能相互沟通、相互影响中发挥着重要作用。在脑肠轴中，肠道微生物具有媒介作用，肠道微生物群可以通过调节营养物质代谢和合成分泌神经递质等途径来影响大脑的发育和功能。同时脑肠轴也参与多种中枢神经系统疾病的发生发展，如创伤性脑损伤、脑血管疾病、胶质瘤、阿尔茨海默病、抑郁症等疾病。本文将对脑肠轴作为中枢神经系统疾病治疗靶点进行综述如下。
Abstract: The brain-gut axis is composed of two-way information exchange between the gastrointestinal tract and the central nervous system, and plays an important role in the communication and mutual influence between the emotional and cognitive center of the brain and the peripheral intestinal function. In the brain-gut axis, gut microbes play a mediating role, and gut microbiota can affect brain development and function by regulating nutrient metabolism and synthesizing and secreting neurotransmitters. At the same time, the brain-gut axis is also involved in the occurrence and development of various central nervous system diseases, such as traumatic brain injury, cer-ebrovascular disease, glioma, Alzheimer’s disease, depression and other diseases. In this paper, the brain-gut axis as a therapeutic target for central nervous system diseases is reviewed as follows.
文章引用：安刚, 宋慧敏, 崔昌萌. 脑肠轴作为中枢神经系统疾病治疗靶点的研究进展[J]. 临床医学进展, 2023, 13(3): 3475-3480. https://doi.org/10.12677/ACM.2023.133496

参考文献

[1] Socała, K., Doboszewska, U., Szopa, A., Serefko, A., Włodarczyk, M., Zielińska, A., Poleszak, E., Fichna, J. and Wlaź, P. (2021) The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders. Pharmacological Research, 172, Article ID: 105840. [Google Scholar] [CrossRef] [PubMed]
[2] Liu, X., Zhao, Z., Ji, R., Zhu, J., Sui, Q.-Q., Knight, G.E., Burnstock, G., He, C., Yuan, H. and Xiang, Z. (2017) Inhibition of P2X7 Receptors Im-proves Outcomes after Traumatic Brain Injury in Rats. Purinergic Signalling, 13, 529-544. [Google Scholar] [CrossRef] [PubMed]
[3] Li, H., Sun, J., Du, J., Wang, F., Fang, R., Yu, C., Xiong, J., Chen, W., Lu, Z. and Liu, J. (2018) Clostridium butyricum Exerts a Neuroprotective Effect in a Mouse Model of Traumatic Brain Injury via the Gut-Brain Axis. Neurogastroenterology & Motility, 30, e13260. [Google Scholar] [CrossRef] [PubMed]
[4] Zhao, Y.F., Wei, D.N. and Tang, Y. (2021) Gut Microbiota Regulate Astrocytic Functions in the Brain: Possible Therapeutic Consequences. Current Neuropharmacology, 19, 1354-1366. [Google Scholar] [CrossRef] 
[5] Ma, Y., Liu, T., Fu, J., Fu, S., Hu, C., Sun, B., Fan, X. and Zhu, J. (2019) Lactobacillus acidophilus Exerts Neuroprotective Effects in Mice with Traumatic Brain Injury. The Journal of Nutrition, 149, 1543-1552. [Google Scholar] [CrossRef] [PubMed]
[6] Ma, E.L., Smith, A.D., Desai, N., Cheung, L., Hanscom, M., Stoica, B.A., Loane, D.J., Shea-Donohue, T. and Faden, A.I. (2017) Bidirectional Brain-Gut Interactions and Chronic Pathological Changes after Traumatic Brain Injury in Mice. Brain, Behavior, and Immunity, 66, 56-69. [Google Scholar] [CrossRef] [PubMed]
[7] Mossad, O. and Erny, D. (2020) The Microbiota-Microglia Axis in Central Nervous System Disorders. Brain Pathology, 30, 1159-1177. [Google Scholar] [CrossRef] [PubMed]
[8] Karve, I.P., Taylor, J.M. and Crack, P.J. (2016) The Contribution of Astrocytes and Microglia to Traumatic Brain Injury. British Journal of Pharmacology, 173, 692-702. [Google Scholar] [CrossRef] [PubMed]
[9] Pluta, R., Januszewski, S. and Czuczwar, S.J. (2021) The Role of Gut Microbiota in an Ischemic Stroke. International Journal of Molecular Sciences, 22, Article No. 915. [Google Scholar] [CrossRef] [PubMed]
[10] Benakis, C., Brea, D., Caballero, S., Faraco, G., Moore, J., Murphy, M., Sita, G., Racchumi, G., Ling, L., Pamer, E.G., Iadecola, C. and Anrather, J. (2016) Commensal Microbiota Affects Ischemic Stroke Outcome by Regulating Intestinal γδ T Cells. Nature Medicine, 22, 516-523. [Google Scholar] [CrossRef] [PubMed]
[11] Dong, X., Zhang, X., Li, C., Chen, J., Xia, S., Bao, X., Ge, J., Cao, X. and Xu, Y. (2022) γδ T Cells Aggravate Blood-Brain-Barrier Injury via IL-17A in Experimental Ischemic Stroke. Neurosci-ence Letters, 776, Article ID: 136563. [Google Scholar] [CrossRef] [PubMed]
[12] Haghikia, A., Li, X.S., Liman, T.G., Bledau, N., Schmidt, D., Zimmermann, F., Kränkel, N., Widera, C., Sonnenschein, K., Haghikia, A., Weissenborn, K., Fraccarollo, D., Heimesaat, M.M., Bauersachs, J., Wang, Z., Zhu, W., Bavendiek, U., Hazen, S.L., Endres, M. and Landmesser, U. (2018) Gut Microbiota-Dependent Trimethylamine N-Oxide Predicts Risk of Cardiovascular Events in Patients with Stroke and Is Related to Proinflammatory Monocytes. Arteriosclerosis, Thrombosis, and Vascular Biology, 38, 2225-2235. [Google Scholar] [CrossRef] 
[13] Cheng, X., Qiu, X., Liu, Y., Yuan, C. and Yang, X. (2019) Trimethylamine N-Oxide Promotes Tissue Factor Expression and Activity in Vascular Endothelial Cells: A New Link Between Trimethylamine N-Oxide and Atherosclerotic Thrombosis. Thrombosis Research, 177, 110-116. [Google Scholar] [CrossRef] [PubMed]
[14] Peh, A., O’Donnell, J.A., Broughton, B.R.S. and Marques, F.Z. (2022) Gut Microbiota and Their Metabolites in Stroke: A Double-Edged Sword. Stroke, 53, 1788-1801. [Google Scholar] [CrossRef] 
[15] Singh, V., Sadler, R., Heindl, S., Llovera, G., Roth, S., Benakis, C. and Liesz, A. (2018) TThe Gut Microbiome Primes a Cerebroprotective Immune Response after Stroke. Journal of Cerebral Blood Flow & Metabolism, 38, 1293-1298. [Google Scholar] [CrossRef] 
[16] Spychala, M.S., Venna, V.R., Jandzinski, M., Doran, S.J., Durgan, D.J., Ganesh, B.P., Ajami, N.J., Putluri, N., Graf, J., Bryan, R.M. and McCullough, L.D. (2018) Age-Related Changes in the Gut Microbiota Influence Systemic Inflammation and Stroke Outcome. Annals of Neurology, 84, 23-36. [Google Scholar] [CrossRef] [PubMed]
[17] Zaragoza-Ojeda, M., Apatiga-Vega, E. and Arenas-Huertero, F. (2021) Role of Aryl Hydrocarbon Receptor in Central Nervous System Tumors: Biological and Therapeutic Implications (Re-view). Oncology Letters, 21, Article No. 460. [Google Scholar] [CrossRef] [PubMed]
[18] Gutiérrez-Vázquez, C. and Quintana, F.J. (2018) Regulation of the Immune Response by the Aryl Hydrocarbon Receptor. Immunity, 48, 19-33. [Google Scholar] [CrossRef] [PubMed]
[19] Takenaka, M.C., Gabriely, G., Rothhammer, V., Mascanfroni, I.D., Wheeler, M.A., Chao, C.C., Gutiérrez-Vázquez, C., Kenison, J., Tjon, E.C., Barroso, A., Vandeventer, T., de Lima, K.A., Rothweiler, S., Mayo, L., Ghannam, S., Zandee, S., Healy, L., Sherr, D., Farez, M.F., Prat, A., et al. (2019) Control of Tumor-Associated Macrophages and T Cells in Glioblastoma via AHR and CD39. Nature Neuroscience, 22, 729-740. [Google Scholar] [CrossRef] [PubMed]
[20] Mazzone, A., Gibbons, S.J., Eisenman, S.T., Strege, P.R., Zheng, T., D’Amato, M., Ordog, T., Fernandez-Zapico, M.E. and Farrugia, G. (2019) Direct Repression of Anoctamin 1 (ANO1) Gene Transcription by Gli Proteins. The FASEB Journal, 33, 6632-6642. [Google Scholar] [CrossRef] 
[21] Kim, H.-J., Kim, J.-Y., Jung, C.-W., Lee, Y.-S., An, J.-Y., Kim, E.H., Kim, K.-H., Lee, S.P., Park, J.-Y. and Park, M.-J. (2021) ANO1 Regulates the Maintenance of Stemness in Glioblastoma Stem Cells by Stabilizing EGFRvIII. Oncogene, 40, 1490-1502. [Google Scholar] [CrossRef] [PubMed]
[22] Zhuang, Z.-Q., Shen, L.-L., Li, W.-W., Fu, X., Zeng, F., Gui, L., Lü, Y., Cai, M., Zhu, C., Tan, Y.-L., Zheng, P., Li, H.-Y., Zhu, J., Zhou, H.-D., Bu, X.-L. and Wang, Y.-J. (2018) Gut Microbiota Is Altered in Patients with Alzheimer’s Disease. Journal of Alzheimer’s Disease, 63, 1337-1346. [Google Scholar] [CrossRef] 
[23] Macfarlane, G.T. and Macfarlane, S. (2012) Bacteria, Colonic Fermen-tation, and Gastrointestinal Health. Journal of AOAC International, 95, 50-60. [Google Scholar] [CrossRef] 
[24] Vijay, N. and Morris, M.E. (2014) Role of Monocarboxylate Transporters in Drug Delivery to the Brain. Current Pharmaceutical Design, 20, 1487-1498. [Google Scholar] [CrossRef] [PubMed]
[25] Govindarajan, N., Agis-Balboa, R.C., Walter, J., Sananbenesi, F. and Fischer, A. (2011) Sodium Butyrate Improves Memory Function in an Alzheimer’s Disease Mouse Model When Administered at an Advanced Stage of Disease Progression. Journal of Alzheimer’s Disease, 26, 187-197. [Google Scholar] [CrossRef] 
[26] Bourassa, M.W., Alim, I., Bultman, S.J. and Ratan, R.R. (2016) Butyrate, Neuroepigenetics and the Gut Microbiome: Can a High Fiber Diet Improve Brain Health? Neuroscience Letters, 625, 56-63. [Google Scholar] [CrossRef] [PubMed]
[27] Erny, D., Hrabě de Angelis, A.L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., Schwierzeck, V., Utermöhlen, O., Chun, E., Garrett, W.S., McCoy, K.D., Diefenbach, A., Staeheli, P., Stecher, B., Amit, I. and Prinz, M. (2015) Host Microbiota Constantly Control Maturation and Function of Microglia in the CNS. Nature Neuroscience, 18, 965-977. [Google Scholar] [CrossRef] [PubMed]
[28] Doens, D. and Fernández, P.L. (2014) Microglia Receptors and Their Im-plications in the Response to Amyloid β for Alzheimer’s Disease Pathogenesis. Journal of Neuroinflammation, 11, Ar-ticle No. 48. [Google Scholar] [CrossRef] [PubMed]
[29] Cryan, J.F. and Slattery, D.A. (2007) Animal Models of Mood Disorders: Recent Developments. Current Opinion in Psychiatry, 20, 1-7. [Google Scholar] [CrossRef] 
[30] 陶伟伟, 董宇, 刘立, 肖东, 吴浩然, 吴颢昕, 陈刚, 狄留庆, 王汉卿. 基于“脑-肠”轴的肠道菌群影响抑郁症研究进展[J]. 南京中医药大学学报, 2019, 35(2): 234-240. [Google Scholar] [CrossRef] 
[31] Ait-Belgnaoui, A., Colom, A., Braniste, V., Ramalho, L., Marrot, A., Cartier, C., Houdeau, E., Theodorou, V. and Tompkins, T. (2014) Probiotic Gut Effect Prevents the Chronic Psychological Stress-Induced Brain Activity Abnormality in Mice. Neurogastroenterology & Motility, 26, 510-520. [Google Scholar] [CrossRef] [PubMed]
[32] Wallace, C.J.K., Foster, J.A., Soares, C.N. and Milev, R.V. (2020) The Effects of Probiotics on Symptoms of Depression: Protocol for a Double-Blind Randomized Place-bo-Controlled Trial. Neuropsychobiology, 79, 108-116. [Google Scholar] [CrossRef] [PubMed]

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