肠道菌群与药物成瘾及相关神经精神疾病关系的研究进展
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摘要
药物成瘾不仅严重损害成瘾者自身健康,还造成了巨大的社会经济负担。吸毒人数不断攀升,复吸率居高不下,严重威胁公共安全。药物成瘾是一种慢性脑病,替代药物治疗如美沙酮,非药物治疗如手术治疗、正念疗法、重复经颅磁刺激等,均不能有效降低成瘾者的心理渴求。目前药物成瘾的治疗方法存在很大局限性,治愈后复吸率高。寻找新的治疗药物和方法仍是药物成瘾的重要课题。近年来,肠道菌群与神经精神疾病相关的研究被大量报道,逐渐揭示了肠道菌群与中枢神经系统之间的联系,随着"微生物-肠-脑轴"的发现,肠道菌群在药物成瘾相关方面的研究也逐渐受到关注,通过查阅国内外文献,该文对肠道菌群与药物成瘾、肠道菌群与神经精神疾病的关系研究进展进行综述。
Drug addiction has not only seriously damaged the addicts′ health, but also caused a huge social and economic burden, threatening public safety. Meanwhile, the number of drug addicts continues to rise and the relapse rate remains high. Actually drug addiction is a kind of chronic brain disease. It is of no avail to reduce the psychological requirement of addicts via alternative drug treatments such as methadone, non-pharmacological treatments, surgical treatment, mindfulness therapy, and repeated transcranial magnetic stimulation etc. In fact, the rate of relapse is still high, accompanied by a series of huge limitations. Therefore, it is of great importance to find new therapeutic drugs and methods for drug addiction. In recent years, numerous studies of intestinal flora and neuropsychiatric diseases have been reported, gradually revealing the link between the intestinal microbiota and the nervous system. With the discovery of the "microbiota-gut-brain axis", the effect of gut microbiota on related aspects of drug addiction has won increasing attention. As a result, this thesis will review the research progress of the relationship between gut microbiota, neuropsychiatric diseases and drug addiction by means of looking up domestic and foreign documents.
Drug addiction has not only seriously damaged the addicts′ health, but also caused a huge social and economic burden, threatening public safety. Meanwhile, the number of drug addicts continues to rise and the relapse rate remains high. Actually drug addiction is a kind of chronic brain disease. It is of no avail to reduce the psychological requirement of addicts via alternative drug treatments such as methadone, non-pharmacological treatments, surgical treatment, mindfulness therapy, and repeated transcranial magnetic stimulation etc. In fact, the rate of relapse is still high, accompanied by a series of huge limitations. Therefore, it is of great importance to find new therapeutic drugs and methods for drug addiction. In recent years, numerous studies of intestinal flora and neuropsychiatric diseases have been reported, gradually revealing the link between the intestinal microbiota and the nervous system. With the discovery of the "microbiota-gut-brain axis", the effect of gut microbiota on related aspects of drug addiction has won increasing attention. As a result, this thesis will review the research progress of the relationship between gut microbiota, neuropsychiatric diseases and drug addiction by means of looking up domestic and foreign documents.
引文
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[2] De Palma G, Collins S M, Bercik P. The microbiota-gut-brain axis in functional gastrointestinal disorders[J].Gut Microbes, 2014, 5(3): 419-29.
[3] Hsiao E Y, McBride S W, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders[J].Cell, 2013, 155(7): 1451-63.
[4] Cryan J F, Dinan T G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour[J].Nat Rev Neurosci, 2012, 13(10): 701-12.
[5] Bravo J A, Forsythe P, Chew M V, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve[J].Proc Natl Acad Sci USA, 2011, 108(38): 16050-5.
[6] Alcock J, Maley C C, Aktipis C A. Is eating behavior manipulated by the gastrointestinal microbiota evolutionary pressures and potential mechanisms[J]. Bioessays, 2014, 36(10):940-9.
[7] Rush A J, Trivedi M H, Wisniewski S R, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report[J]. Am J Psychiatry,2006, 163(11):1905-17.
[8] Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder[J].Brain Behav Immun, 2015, 48:186-94.
[9] 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, 82:109-18.
[10] Zheng P, Zeng B, Zhou C, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host′s metabolism[J].Mol Psychiatry, 2016, 21(6): 786-96.
[11] Finegold S M, Dowd S E, Gontcharova V, et al. Pyrosequencing study of fecal microflora of autistic and control children[J].Anaerobe, 2010, 16(4): 444-53.
[12] 吴文宝,孔庆宏,阚祥绪,等. 凋亡通路及caspases在阿尔茨海默病中作为治疗靶点的研究[J]. 中国药理学通报, 2015, 31(11):1496-501. Wu W B, Kong Q H, Kan X X, et al. Research progress of apoptosis pathways and caspases as therapeutic targets involved in Alzheimer′s disease[J]. Chin Pharmacol Bull, 2015, 31(11):1496-501.
[13] Zhang L, Wang Y, Xiayu X, et al. Altered gut microbiota in a mouse model of Alzheimer′s disease[J].J Alzheimers Dis, 2017, 60(4): 1241-57.
[14] Matsumoto M, Benno Y. Consumption of Bifidobacterium lactis LKM512 yogurt reduces gut mutagenicity by increasing gut polyamine contents in healthy adult subjects[J].Mutat Res, 2004, 568(2):147-53.
[15] 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):666-73.
[16] Scheperjans F, Aho V, Pereira P A, et al. Gut microbiota are related to Parkinson′s disease and clinical phenotypes[J]. Mov Disord, 2015,30(3):350-8.
[17] Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome[J].Nature, 2011,473(7346):174-80.
[18] Compton W M, Conway K P, Stinson F S, et al. Changes in the prevalence of major depression and comorbid substance use disorders in the United States between 1991-1992 and 2001-2002[J]. Am J Psychiatry,2006,163:2141-7.
[19] Leclercq S, Matamoros S, Cani P D, et al. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity[J]. Proc Natl Acad Sci USA, 2014, 111(42): E4485-93.
[20] Abulseoud O A, Camsari U M, Ruby C L, et al. Attenuation of ethanol withdrawal by ceftriaxone-induced upregulation of glutamate transporter EAAT2[J].Neuropsychopharmacology, 2014, 39(7): 1674-84.
[21] Xiao H, Ge C, Feng G, et al. Gut microbiota modulates alcohol withdrawal-induced anxiety in mice[J].Toxicol Lett, 2018, 287: 23-30.
[22] Peterson V L, Jury N J, Cabrera-Rubio R, et al. Drunk bugs: chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice[J].Behav Brain Res, 2017, 323:172-6.
[23] Ning T, Gong X, Xie L, et al. Gut microbiota analysis in rats with methamphetamine-induced conditioned place preference[J].Front Microbiol, 2017, 8:1620-8.
[24] Volpe G E, Ward H, Mwamburi M, et al. Associations of cocaine use and HIV infection with the intestinal microbiota, microbial translocation, and inflammation[J]. J Stud Alcohol Drugs, 2014,75(2):347-57.
[25] Kiraly D D, Walker D M, Calipari E S, et al. Alterations of the host microbiome affect behavioral responses to cocaine[J].Sci Rep, 2016, 6: 35455.
[2] De Palma G, Collins S M, Bercik P. The microbiota-gut-brain axis in functional gastrointestinal disorders[J].Gut Microbes, 2014, 5(3): 419-29.
[3] Hsiao E Y, McBride S W, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders[J].Cell, 2013, 155(7): 1451-63.
[4] Cryan J F, Dinan T G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour[J].Nat Rev Neurosci, 2012, 13(10): 701-12.
[5] Bravo J A, Forsythe P, Chew M V, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve[J].Proc Natl Acad Sci USA, 2011, 108(38): 16050-5.
[6] Alcock J, Maley C C, Aktipis C A. Is eating behavior manipulated by the gastrointestinal microbiota evolutionary pressures and potential mechanisms[J]. Bioessays, 2014, 36(10):940-9.
[7] Rush A J, Trivedi M H, Wisniewski S R, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report[J]. Am J Psychiatry,2006, 163(11):1905-17.
[8] Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder[J].Brain Behav Immun, 2015, 48:186-94.
[9] 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, 82:109-18.
[10] Zheng P, Zeng B, Zhou C, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host′s metabolism[J].Mol Psychiatry, 2016, 21(6): 786-96.
[11] Finegold S M, Dowd S E, Gontcharova V, et al. Pyrosequencing study of fecal microflora of autistic and control children[J].Anaerobe, 2010, 16(4): 444-53.
[12] 吴文宝,孔庆宏,阚祥绪,等. 凋亡通路及caspases在阿尔茨海默病中作为治疗靶点的研究[J]. 中国药理学通报, 2015, 31(11):1496-501. Wu W B, Kong Q H, Kan X X, et al. Research progress of apoptosis pathways and caspases as therapeutic targets involved in Alzheimer′s disease[J]. Chin Pharmacol Bull, 2015, 31(11):1496-501.
[13] Zhang L, Wang Y, Xiayu X, et al. Altered gut microbiota in a mouse model of Alzheimer′s disease[J].J Alzheimers Dis, 2017, 60(4): 1241-57.
[14] Matsumoto M, Benno Y. Consumption of Bifidobacterium lactis LKM512 yogurt reduces gut mutagenicity by increasing gut polyamine contents in healthy adult subjects[J].Mutat Res, 2004, 568(2):147-53.
[15] 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):666-73.
[16] Scheperjans F, Aho V, Pereira P A, et al. Gut microbiota are related to Parkinson′s disease and clinical phenotypes[J]. Mov Disord, 2015,30(3):350-8.
[17] Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome[J].Nature, 2011,473(7346):174-80.
[18] Compton W M, Conway K P, Stinson F S, et al. Changes in the prevalence of major depression and comorbid substance use disorders in the United States between 1991-1992 and 2001-2002[J]. Am J Psychiatry,2006,163:2141-7.
[19] Leclercq S, Matamoros S, Cani P D, et al. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity[J]. Proc Natl Acad Sci USA, 2014, 111(42): E4485-93.
[20] Abulseoud O A, Camsari U M, Ruby C L, et al. Attenuation of ethanol withdrawal by ceftriaxone-induced upregulation of glutamate transporter EAAT2[J].Neuropsychopharmacology, 2014, 39(7): 1674-84.
[21] Xiao H, Ge C, Feng G, et al. Gut microbiota modulates alcohol withdrawal-induced anxiety in mice[J].Toxicol Lett, 2018, 287: 23-30.
[22] Peterson V L, Jury N J, Cabrera-Rubio R, et al. Drunk bugs: chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice[J].Behav Brain Res, 2017, 323:172-6.
[23] Ning T, Gong X, Xie L, et al. Gut microbiota analysis in rats with methamphetamine-induced conditioned place preference[J].Front Microbiol, 2017, 8:1620-8.
[24] Volpe G E, Ward H, Mwamburi M, et al. Associations of cocaine use and HIV infection with the intestinal microbiota, microbial translocation, and inflammation[J]. J Stud Alcohol Drugs, 2014,75(2):347-57.
[25] Kiraly D D, Walker D M, Calipari E S, et al. Alterations of the host microbiome affect behavioral responses to cocaine[J].Sci Rep, 2016, 6: 35455.