吉林大学学报(医学版) ›› 2022, Vol. 48 ›› Issue (4): 1094-1100.doi: 10.13481/j.1671-587X.20220434
• 综述 • 上一篇
收稿日期:2021-06-24
出版日期:2022-07-28
发布日期:2022-07-26
通讯作者:
陈金波
E-mail:chenjinbo6720@126.com
作者简介:王凯新(1986-),女,山东省济南市人,在读硕士研究生,主要从事抑郁症基础和临床方面的研究。
基金资助:
Received:2021-06-24
Online:2022-07-28
Published:2022-07-26
摘要:
人体的肠道菌群是一个数量巨大的动态种群合集,且在每个个体中都是独一无二的。肠道菌群的定植从怀孕期间开始,分娩后受药物、饮食和压力等因素影响形成了个体的菌群差异,并随着时间推移大多数菌群结构保持稳定。随着对肠道菌群研究的不断深入,越来越多的证据显示:肠道菌群与抑郁障碍有密切关联,该关联源于肠道和大脑之间的双向通信系统,称为肠道菌群-肠道-脑 (MGB)轴, MGB轴在维持大脑和肠道的正常功能中发挥着重要作用,其作用机制可能涉及下丘脑-垂体-肾上腺(HPA)轴、中枢神经系统、肠神经系统、免疫系统、神经递质、神经调节物质、肠黏膜屏障和血脑屏障途径。基于肠道菌群与抑郁症的密切关系,如何逆转肠道菌群失调成为目前研究的重点。肠道菌群干预治疗,即通过益生元、益生菌和粪菌移植(FMT)等方法来改善肠道菌群状态,可能为抑郁症提供一种有前景的治疗方法。现对肠道菌群与抑郁症之间的相互影响、肠道菌群失调在抑郁症发病中的可能机制和肠道菌群干预治疗抑郁症的初步尝试进行全面综述,旨在更好地了解肠道菌群与抑郁症的关系,为探索抑郁症的防治提供新靶点和新思路。
中图分类号:
王凯新,董晓梦,苏毅鹏,陈金波. 肠道菌群与抑郁症关系的研究进展[J]. 吉林大学学报(医学版), 2022, 48(4): 1094-1100.
| 1 | DEAN J, KESHAVAN M. The neurobiology of depression: an integrated view[J]. Asian J Psychiatr, 2017, 27: 101-111. |
| 2 | WALLACE C J K, MILEV R. The effects of probiotics on depressive symptoms in humans: a systematic review[J]. Ann Gen Psychiatry, 2017, 16: 14. |
| 3 | CRUZ-PEREIRA J S, REA K, NOLAN Y M, et al. Depression’s unholy trinity: dysregulated stress, immunity, and the microbiome[J]. Annu Rev Psychol, 2020, 71: 49-78. |
| 4 | LACH G, SCHELLEKENS H, DINAN T G, et al. Anxiety, depression, and the microbiome: a role for gut peptides[J]. Neurotherapeutics, 2018, 15(1): 36-59. |
| 5 | GOLOFAST B, VALES K. The connection between microbiome and schizophrenia[J]. Neurosci Biobehav Rev, 2020, 108: 712-731. |
| 6 | IMOTO N, KANO C, AOYAGI Y, et al. Administration of β-lactam antibiotics and delivery method correlate with intestinal abundances of Bifidobacteria and Bacteroides in early infancy, in Japan[J]. Sci Rep, 2021, 11(1): 6231. |
| 7 | BELKAID Y, HAND T W. Role of the microbiota in immunity and inflammation[J]. Cell, 2014, 157(1): 121-141. |
| 8 | FRÖHLICH E E, FARZI A, MAYERHOFER R,et al.Cognitive impairment by antibiotic-induced gut dysbiosis: analysis of gut microbiota-brain communication[J].Brain Behav Immun,2016,56:140-155. |
| 9 | WANG P, TU K, CAO P, et al. Antibiotics-induced intestinal dysbacteriosis caused behavioral alternations and neuronal activation in different brain regions in mice[J]. Mol Brain, 2021, 14(1): 49. |
| 10 | RINNINELLA E, RAOUL P, CINTONI M, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases[J]. Microorganisms, 2019, 7(1): E14. |
| 11 | WINTHER G, PYNDT JØRGENSEN B M, ELFVING B, et al. Dietary magnesium deficiency alters gut microbiota and leads to depressive-like behaviour[J]. Acta Neuropsychiatr, 2015, 27(3): 168-176. |
| 12 | LYTE J M. Eating for 3.8 × 1013: examining the impact of diet and nutrition on the microbiota-gut-brain axis through the lens of microbial endocrinology[J]. Front Endocrinol (Lausanne), 2018, 9: 796. |
| 13 | PROVENSI G, SCHMIDT S D, BOEHME M, et al. Preventing adolescent stress-induced cognitive and microbiome changes by diet[J]. Proc Natl Acad Sci U S A, 2019, 116(19): 9644-9651. |
| 14 | MCCARTHY M M, NUGENT B M, LENZ K M. Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain[J]. Nat Rev Neurosci, 2017, 18(8): 471-484. |
| 15 | JAGGAR M, REA K, SPICHAK S, et al. You’ve got male: sex and the microbiota-gut-brain axis across the lifespan[J]. Front Neuroendocrinol, 2020, 56: 100815. |
| 16 | AUDET M C. Stress-induced disturbances along the gut microbiota-immune-brain axis and implications for mental health: does sex matter? [J]. Front Neuroendocrinol, 2019, 54: 100772. |
| 17 | CASPANI G, KENNEDY S, FOSTER J A, et al. Gut microbial metabolites in depression: understanding the biochemical mechanisms[J]. Microb Cell,2019,6(10): 454-481. |
| 18 | RINCEL M, AUBERT P, CHEVALIER J, et al. Multi-hit early life adversity affects gut microbiota, brain and behavior in a sex-dependent manner[J]. Brain Behav Immun, 2019, 80: 179-192. |
| 19 | ZHANG Y, HUANG R R, CHENG M J, et al. Gut microbiota from NLRP3-deficient mice ameliorates depressive-like behaviors by regulating astrocyte dysfunction via circHIPK2 [J].Microbiome,2019,7(1):116. |
| 20 | ZHANG K, FUJITA Y, CHANG L J, et al. Abnormal composition of gut microbiota is associated with resilience versus susceptibility to inescapable electric stress[J]. Transl Psychiatry, 2019, 9(1): 231. |
| 21 | CHUNG Y E, CHEN H C, CHOU H L, et al. Exploration of microbiota targets for major depressive disorder and mood related traits[J]. J Psychiatr Res, 2019, 111: 74-82. |
| 22 | RONG H, XIE X H, ZHAO J, et al. Similarly in depression, nuances of gut microbiota: Evidences from a shotgun metagenomics sequencing study on major depressive disorder versus bipolar disorder with current major depressive episode patients[J]. J Psychiatr Res, 2019, 113: 90-99. |
| 23 | CHEN Z, LI J, GUI S W, et al. Comparative metaproteomics analysis shows altered fecal microbiota signatures in patients with major depressive disorder[J]. Neuroreport, 2018, 29(5): 417-425. |
| 24 | CHEN J J, ZHENG P, LIU Y Y, et al. Sex differences in gut microbiota in patients with major depressive disorder[J]. Neuropsychiatr Dis Treat, 2018, 14: 647-655. |
| 25 | PEARSON-LEARY J, ZHAO C Y, BITTINGER K, et al. The gut microbiome regulates the increases in depressive-type behaviors and in inflammatory processes in the ventral hippocampus of stress vulnerable rats[J]. Mol Psychiatry, 2020, 25(5): 1068-1079. |
| 26 | KAZEMI A, NOORBALA A A, AZAM K, et al. Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: a randomized clinical trial[J]. Clin Nutr, 2019, 38(2): 522-528. |
| 27 | KARAKULA-JUCHNOWICZ H, ROG J, JUCHNOWICZ D, et al. The study evaluating the effect of probiotic supplementation on the mental status, inflammation, and intestinal barrier in major depressive disorder patients using gluten-free or gluten-containing diet (SANGUT study): a 12-week, randomized, double-blind, and placebo-controlled clinical study protocol[J]. Nutr J, 2019, 18(1): 50. |
| 28 | 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): 786-796. |
| 29 | MOHAJERI M H, GLA FATA, STEINERT R E,et al.Relationship between the gut microbiome and brain function[J]. Nutr Rev, 2018, 76(7): 481-496. |
| 30 | KUNDU P, BLACHER E, ELINAV E, et al. Our gut microbiome: the evolving inner self[J]. Cell, 2017,171(7): 1481-1493. |
| 31 | BARDEN N. Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression[J]. J Psychiatry Neurosci, 2004, 29(3): 185-193. |
| 32 | SUDO N, CHIDA Y, AIBA Y J, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice[J]. J Physiol, 2004, 558(Pt 1): 263-275. |
| 33 | BANKS W A. Blood-brain barrier transport of cytokines: a mechanism for neuropathology[J]. Curr Pharm Des, 2005, 11(8): 973-984. |
| 34 | PARASHAR A, UDAYABANU M. Gut microbiota regulates key modulators of social behavior[J]. Eur Neuropsychopharmacol, 2016, 26(1): 78-91. |
| 35 | HERMAN J P, MCKLVEEN J M, GHOSAL S, et al. Regulation of the hypothalamic-pituitary-adrenocortical stress response[J].Compr Physiol,2016,6(2): 603-621. |
| 36 | MOLONEY R D, JOHNSON A C, O'MAHONY S M, et al. Stress and the microbiota-gut-brain axis in visceral pain: relevance to irritable bowel syndrome[J]. CNS Neurosci Ther, 2016, 22(2): 102-117. |
| 37 | KROGH J, BENROS M E, JØRGENSEN M B, et al. The association between depressive symptoms, cognitive function, and inflammation in major depression[J]. Brain Behav Immun, 2014, 35: 70-76. |
| 38 | LANQUILLON S, KRIEG J C, BENING-ABU-SHACH U, et al. Cytokine production and treatment response in major depressive disorder[J]. Neuropsychopharmacology, 2000, 22(4): 370-379. |
| 39 | ROY SARKAR S, BANERJEE S. Gut microbiota in neurodegenerative disorders[J]. J Neuroimmunol, 2019, 328: 98-104. |
| 40 | GILBERT J A, BLASER M J, CAPORASO J G,et al. Current understanding of the human microbiome[J]. Nat Med, 2018, 24(4): 392-400. |
| 41 | ERNY D, HRABĚ DE ANGELIS A L, JAITIN D,et al.Host microbiota constantly control maturation and function of microglia in the CNS[J]. Nat Neurosci, 2015, 18(7): 965-977. |
| 42 | CAMPOS A C, ROCHA N P, NICOLI J R, et al. Absence of gut microbiota influences lipopolysaccharide-induced behavioral changes in mice[J]. Behav Brain Res, 2016, 312: 186-194. |
| 43 | KACIMI R, GIFFARD R G, YENARI M A. Endotoxin-activated microglia injure brain derived endothelial cells via NF-κB, JAK-STAT and JNK stress kinase pathways[J]. J Inflamm (Lond), 2011, 8: 7. |
| 44 | MITTAL R, DEBS L H, PATEL A P, et al. Neurotransmitters: the critical modulators regulating gut-brain axis[J]. J Cell Physiol, 2017, 232(9): 2359-2372. |
| 45 | WINTER G, HART R A, CHARLESWORTH R P G,et al. Gut microbiome and depression: what we know and what we need to know[J]. Rev Neurosci, 2018,29(6): 629-643. |
| 46 | 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. |
| 47 | STRANDWITZ P. Neurotransmitter modulation by the gut microbiota[J].Brain Res, 2018, 1693(Pt B):128-133. |
| 48 | VILLAGELIÚ D, LYTE M. Dopamine production in Enterococcus faecium: a microbial endocrinology-based mechanism for the selection of probiotics based on neurochemical-producing potential[J]. PLoS One, 2018, 13(11): e0207038. |
| 49 | KENNEDY P J, CRYAN J F, DINAN T G, et al. Kynurenine pathway metabolism and the microbiota-gut-brain axis[J]. Neuropharmacology, 2017, 112(Pt B): 399-412. |
| 50 | DE WOUW MVAN, 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. |
| 51 | KELLY C J, ZHENG L, CAMPBELL E L, et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function[J]. Cell Host Microbe, 2015, 17(5): 662-671. |
| 52 | URSELL L K, METCALF J L, PARFREY L W,et al. Defining the human microbiome[J]. Nutr Rev, 2012, 70(): S38-S44. |
| 53 | BOURASSA M W, ALIM I, BULTMAN S J, et al. Butyrate, neuroepigenetics and the gut microbiome: can a high fiber diet improve brain health? [J]. Neurosci Lett, 2016, 625: 56-63. |
| 54 | TIAN P J, WANG G, ZHAO J X, et al. Bifidobacterium with the role of 5-hydroxytryptophan synthesis regulation alleviates the symptom of depression and related microbiota dysbiosis[J]. J Nutr Biochem, 2019, 66: 43-51. |
| 55 | CHANG P V, HAO L M, OFFERMANNS S, et al. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition[J]. Proc Natl Acad Sci USA, 2014,111(6): 2247-2252. |
| 56 | SLYEPCHENKO A, MAES M, JACKA F N, et al. Gut microbiota, bacterial translocation, and interactions with diet: pathophysiological links between major depressive disorder and non-communicable medical comorbidities[J]. Psychother Psychosom, 2017,86(1): 31-46. |
| 57 | PAIVA I H R, DUARTE-SILVA E, PEIXOTO C A. The role of prebiotics in cognition, anxiety, and depression[J]. Eur Neuropsychopharmacol, 2020, 34: 1-18. |
| 58 | BOLLRATH J, ImmunologyPOWRIE F. Feed your Tregs more fiber[J]. Science, 2013, 341(6145): 463-464. |
| 59 | SWANSON K S, GIBSON G R, HUTKINS R, et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics[J]. Nat Rev Gastroenterol Hepatol, 2020, 17(11): 687-701. |
| 60 | GUO Y, XIE J P, DENG K, et al. Prophylactic effects of Bifidobacterium adolescentis on anxiety and depression-like phenotypes after chronic stress: a role of the gut microbiota-inflammation axis[J]. Front Behav Neurosci, 2019, 13: 126. |
| 61 | BAMBLING M, EDWARDS S C, HALL S, et al. A combination of probiotics and magnesium orotate attenuate depression in a small SSRI resistant cohort: an intestinal anti-inflammatory response is suggested[J]. Inflammopharmacology, 2017, 25(2): 271-274. |
| 62 | FOND G B, LAGIER J C, HONORE S, et al. Microbiota-orientated treatments for major depression and schizophrenia[J]. Nutrients, 2020, 12(4): E1024. |
| 63 | KILINÇARSLAN S, EVRENSEL A. The effect of fecal microbiota transplantation on psychiatric symptoms among patients with inflammatory bowel disease: an experimental study[J]. Actas Esp Psiquiatr,2020,48(1): 1-7. |
| 64 | CAI T, SHI X, YUAN L Z, et al. Fecal microbiota transplantation in an elderly patient with mental depression[J]. Int Psychogeriatr, 2019, 31(10): 1525-1526. |
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