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人体表面及内部生活着数量巨大、种类多样的微生物,其中绝大部分是由细菌菌群组成的。肠道微生物和中枢神经系统之间存在相互作用,肠道微生物的异常可以通过“菌-肠-脑”轴参与到机体认知和社会行为等的复杂调控中,且已有多项研究发现肠道菌失调与抑郁症的发生密切相关[1],会通过多种不同的方式和途径加速或诱导抑郁症的发生。口服药物治疗是目前常用的方式,可在一定程度上减缓病人症状,但是目前部分抗抑郁药物仍具有一定的局限性[2]。现已有研究发现,益生菌可以通过多重机制来控制抑郁样行为[3],这为我们探索抗抑郁药物的研发提供了一个新的方向。本综述将从抑郁症、肠道菌代谢产物、作用分子水平出发探讨抑郁症的机制,在对现有益生菌生物制剂治疗抑郁症的研究发现的基础上,对肠道菌这一新靶点进行展望,为寻找抗抑郁药物研发的方向提供帮助。
Advances in antidepressant therapy related to gut microbiota
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摘要:
目的 介绍肠道菌群与抑郁症的病理机制以及相关治疗的研究进展,为后续以肠道菌为靶点的抗抑郁药物的研发提供帮助。 方法 查阅近年来肠道菌群与抑郁症方面的33篇中英文文献进行分类总结,从肠道菌群的门、科、属水平的角度探讨了抑郁状态下肠道菌群多样性的变化,从分子水平上阐述了肠道菌与抑郁症发病机制之间的关系,总结现有相关研究,进一步探索以肠道菌群为靶点进行药物研发治疗的可行性。 结果 肠道菌紊乱与抑郁症之间相互作用,现有益生菌等生物制剂可通过改善肠道菌群病理状态下的紊乱对抑郁症治疗起到缓解作用。 结论 肠道菌群失调与抑郁的发生密切相关,以肠道菌为靶点的相关药物研发治疗,可能成为治疗抑郁症的新途径。 Abstract:Objective This paper introduces the research progress on the pathogenesis of depression related to gut microbiota and provides the resources for the subsequent development of antidepressant drugs targeting gut microbiota. Methods 33 literatures on gut microbiota and depression in recent years were reviewed. The changes of gut microbiota diversity under depression were discussed from the perspectives of phylum, family and genus. The relationship between gut microbiota and the pathogenesis of depression was expounded at the molecular level, and the existing relevant studies were summarized. The feasibility of drug development targeting gut microbiota was explored. Results There is a relationship between gut microbiota disorder and depression. Existing biological agents such as probiotics can alleviate depression by adjusting the disorder of gut microbiota. Conclusion The imbalance of gut microbiota is closely related to the occurrence of depression, and the development of drugs targeting gut microbiota may become a new way to treat depression. -
Key words:
- depression /
- gut microbiota /
- microbiome-gut-brain axis
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[1] KELLY J R, BORRE Y, O' BRIEN C, et al. Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat[J]. J Psychiatr Res,2016,82:109-118. doi: 10.1016/j.jpsychires.2016.07.019 [2] 查伟, 李树生, 徐柯, 等. 柴桂温胆定志汤联合帕罗西汀治疗抑郁症疗效和安全性评价[J]. 中国药业, 2019, 28(13):53-55. doi: 10.3969/j.issn.1006-4931.2019.13.016 [3] GILBERT K, ARSENEAULT-BRÉARD J, FLORES MONACO F, et al. Attenuation of post-myocardial infarction depression in rats by n-3 fatty acids or probiotics starting after the onset of reperfusion[J]. Br J Nutr,2013,109(1):50-56. doi: 10.1017/S0007114512003807 [4] ZHUANG F, ZHOU X, GAO X, et al. Cytokines and glucocorticoid receptors are associated with the antidepressant-like effect of alarin[J]. Peptides,2016,76:115-129. doi: 10.1016/j.peptides.2016.01.002 [5] 汪崇泽, 盛国红. 免疫炎症途径与抑郁症的研究进展[J]. 精神医学杂志, 2015, 28(5):397-400. doi: 10.3969/j.issn.2095-9346.2015.05.025 [6] AAN HET ROT M, MATHEW S J, CHARNEY D S. Neurobiological mechanisms in major depressive disorder[J]. CMAJ,2009,180(3):305-313. doi: 10.1503/cmaj.080697 [7] HAMON M, BLIER P. Monoamine neurocircuitry in depression and strategies for new treatments[J]. Prog Neuropsychopharmacol Biol Psychiatry,2013,45:54-63. doi: 10.1016/j.pnpbp.2013.04.009 [8] PYTKA K, DZIUBINA A, MŁYNIEC K, et al. The role of glutamatergic, GABA-ergic, and cholinergic receptors in depression and antidepressant-like effect[J]. Pharmacol Rep,2016,68(2):443-450. doi: 10.1016/j.pharep.2015.10.006 [9] MORAITIS A G, BLOCK T, NGUYEN D, et al. The role of glucocorticoid receptors in metabolic syndrome and psychiatric illness[J]. J Steroid Biochem Mol Biol, 2017, 165(pt a): 114-120. [10] LIU Y X, ZHANG L, WANG X Q, et al. Similar fecal microbiota signatures in patients with diarrhea-predominant irritable bowel syndrome and patients with depression[J]. Clinical Gastroenterology and Hepatology,2016,14(11):1602-1611.e5. doi: 10.1016/j.cgh.2016.05.033 [11] CHEN Z, LI J, GUI S, et al. Comparative metaproteomics analysis shows altered fecal microbiota signatures in patients with major depressive disorder[J]. Neuroreport,2018,29(5):417-425. doi: 10.1097/WNR.0000000000000985 [12] YU M, JIA H, ZHOU C, et al. Variations in gut microbiota and fecal metabolic phenotype associated with depression by 16S rRNA gene sequencing and LC/MS-based metabolomics[J]. J Pharm Biomed Anal,2017,138:231-239. doi: 10.1016/j.jpba.2017.02.008 [13] 刘佳琳. 肠道菌群介导的栀子豉汤抗抑郁作用及配伍机制研究[D]. 上海: 海军军医大学, 2019. [14] JIANG H, LING Z, LING Z, et al. Altered fecal microbiota composition in patients with major depressive disorder[J]. Brain Behav Immun,2015,48:186-194. doi: 10.1016/j.bbi.2015.03.016 [15] RONG HAN. A case-control study on the abundance, species and gene functional pathway of gut microbiota in patients with depression[J]. China Med Abstr Intern Med,2017,34(3):191-192. [16] MESSAOUDI M, LALONDE R, VIOLLE N, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects[J]. Br J Nutr,2011,105(5):755-764. doi: 10.1017/S0007114510004319 [17] VAN DE WOUW M, BOEHME M, LYTE J M, et al. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations[J]. J Physiol,2018,596(20):4923-4944. doi: 10.1113/JP276431 [18] CHEN J J, ZHOU C J, LIU Z, et al. Divergent urinary metabolic phenotypes between major depressive disorder and bipolar disorder identified by a combined GC–MS and NMR spectroscopic metabonomic approach[J]. J Proteome Res,2015,14(8):3382-3389. doi: 10.1021/acs.jproteome.5b00434 [19] CORRÊA-OLIVEIRA R, FACHI J L, VIEIRA A, et al. Regulation of immune cell function by short-chain fatty acids[J]. Clin Trans Immunol,2016,5(4):e73. doi: 10.1038/cti.2016.17 [20] SCHROEDER F A, LIN C L, CRUSIO W E, et al. Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse[J]. Biological psychiatry,2007,62(1):55-64. doi: 10.1016/j.biopsych.2006.06.036 [21] YAMAWAKI Y, YOSHIOKA N, NOZAKI K, et al. Sodium butyrate abolishes lipopolysaccharide-induced depression-like behaviors and hippocampal microglial activation in mice[J]. Brain Res,2018,1680:13-38. doi: 10.1016/j.brainres.2017.12.004 [22] NANKOVA B B, AGARWAL R, MACFABE D F, et al. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells - possible relevance to autism spectrum disorders[J]. PLoS One,2014,9(8):e103740. doi: 10.1371/journal.pone.0103740 [23] VAN DER VEEN F M, EVERS E A, DEUTZ N E, et al. Effects of acute tryptophan depletion on mood and facial emotion perception related brain activation and performance in healthy women with and without a family history of depression[J]. Neuropsychopharmacology,2007,32(1):216-224. doi: 10.1038/sj.npp.1301212 [24] CLARKE G, GRENHAM S, SCULLY P, et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner[J]. Mol Psychiatry,2013,18(6):666-673. doi: 10.1038/mp.2012.77 [25] BHATTACHARYA S K, MITRA S K, ACHARYA S B. Anxiogenic activity of isatin, a putative biological factor, in rodents[J]. J Psychopharmacol,1991,5(3):202-206. doi: 10.1177/026988119100500304 [26] RÍOS-COVIÁN D, RUAS-MADIEDO P, MARGOLLES A, et al. Intestinal short chain fatty acids and their link with diet and human health[J]. Front Microbiol,2016,7:185. [27] LAURITZEN K H, MORLAND C, PUCHADES M, et al. Lactate receptor sites link neurotransmission, neurovascular coupling, and brain energy metabolism[J]. Cerebral Cortex,2014,24(10):2784-2795. doi: 10.1093/cercor/bht136 [28] RUSSELL D W. The enzymes, regulation, and genetics of bile acid synthesis[J]. Annu Rev Biochem,2003,72(1):137-174. doi: 10.1146/annurev.biochem.72.121801.161712 [29] QUINN M, MCMILLIN M, GALINDO C, et al. Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms[J]. Dig Liver Dis,2014,46(6):527-534. doi: 10.1016/j.dld.2014.01.159 [30] RAIMONDI F, SANTORO P, BARONE M V, et al. Bile acids modulate tight junction structure and barrier function of Caco-2 monolayers via EGFR activation[J]. Am J Physiol-Gastrointest Liver Physiol,2008,294(4):G906-G913. doi: 10.1152/ajpgi.00043.2007 [31] MOORE L B, GOODWIN B, JONES S A, et al. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor[J]. PNAS,2000,97(13):7500-7502. doi: 10.1073/pnas.130155097 [32] 安邦, 张大维, 赵珊珊, 等. 双歧杆菌三联活菌辅助帕罗西汀治疗女性抑郁症患者效果观察及机制探讨[J]. 山东医药, 2020, 60(29):58-60. doi: 10.3969/j.issn.1002-266X.2020.29.016 [33] 吴国琳, 余国友, 范小芬, 等. 单味中药及其有效成份对肠道微生态的调节作用研究概况[J]. 中国中医药现代远程教育, 2015, 13(9):134-136. doi: 10.3969/j.issn.1672-2779.2015.09.067
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