上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2021 , Vol. 41 >Issue 7: 967 - 971

DOI: https://doi.org/10.3969/j.issn.1674-8115.2021.07.020

综述

肠道微生物群在强迫症发病机制及治疗中的作用研究进展

  • 张瀛丹 ,
  • 王振
展开
  • 上海交通大学医学院附属精神卫生中心临床心理科，上海 200030
张瀛丹（1997—），女，博士生；电子信箱：erin6529@163.com。

网络出版日期: 2021-08-03

基金资助

上海市优秀学术带头人(20XD1423100);上海市卫生健康委员会重要薄弱学科-心身医学(2019ZB0201)

收起

Research progress of the role of gut microbiota in the pathogenesis and treatment of obsessive-compulsive disorder

  • Ying-dan ZHANG ,
  • Zhen WANG
Expand
  • Department of Clinical Psychology, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China

Online published: 2021-08-03

Supported by

Program of Shanghai Academic Research Leader(20XD1423100);Grants from Shanghai Municipal Health Commission for Key Developing Disciplines-Psychosomatic Medicine Program(2019ZB0201)

Fold

摘要

强迫症是核心表现为反复出现的闯入性想法或重复行为的一种慢性致残性精神障碍，其病因复杂，发病机制尚未被完全阐明。近年来，微生物群-肠-脑（microbiota-gut-brain，MGB）轴成为精神障碍的研究热点。肠道微生物群作为脑-肠双向联系的关键媒介，在免疫炎症、神经内分泌和大脑发育过程中起着重要作用。该文对MGB轴与强迫症可能的关联及由该轴介导的潜在病因学途径进行综述，并针对肠道微生物群这一新靶点的治疗方案进行探讨。

关键词： 强迫症; 微生物群-肠-脑轴; 肠道微生物群

本文引用格式

张瀛丹 , 王振 . 肠道微生物群在强迫症发病机制及治疗中的作用研究进展[J]. 上海交通大学学报（医学版）, 2021 , 41(7) : 967 -971 . DOI: 10.3969/j.issn.1674-8115.2021.07.020

Abstract

Obsessive-compulsive disorder (OCD) is a chronic and disabling psychiatric disorder characterized by recurrent intrusive thoughts or repetitive behaviors. However, the etiology is complex and the underlying pathophysiology remains unclear. In recent years, microbiota-gut-brain (MGB) axis has become a research hotspot in the field of psychiatry. Gut microbiota, as a key medium of the bilateral connection between brain and intestine, plays an important role in immune inflammation, neuroendocrine and brain development. This review illustrates possible link between OCD and MGB axis and the underlying etiological pathway. And treatment options targeting the gut microbiome is also further discussed.

Key words： obsessive-compulsive disorder (OCD); microbiota-gut-brain axis; gut microbiota

参考文献

1 Huang Y, Wang Y, Wang H, et al. Prevalence of mental disorders in China: a cross-sectional epidemiological study[J]. Lancet Psychiatry, 2019, 6(3): 211-224.
2 Robbins TW, Vaghi MM, Banca P. Obsessive-compulsive disorder: puzzles and prospects[J]. Neuron, 2019, 102(1): 27-47.
3 Cryan JF, O′Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis[J]. Physiol Rev, 2019, 99(4): 1877-2013.
4 Kundu P, Blacher E, Elinav E, et al. Our gut microbiome: the evolving inner self[J]. Cell, 2017, 171(7): 1481-1493.
5 Turna J, Grosman Kaplan K, Patterson B, et al. Higher prevalence of irritable bowel syndrome and greater gastrointestinal symptoms in obsessive-compulsive disorder[J]. J Psychiatr Res, 2019, 118: 1-6.
6 Liu YX, Zhang L, Wang XQ, et al. Similar fecal microbiota signatures in patients with diarrhea-predominant irritable bowel syndrome and patients with depression[J]. Clin Gastroenterol Hepatol, 2016, 14(11): 1602-1611.e5.
7 Barzilay R, Patrick A, Calkins ME, et al. Association between early-life trauma and obsessive compulsive symptoms in community youth[J]. Depress Anxiety, 2019, 36(7): 586-595.
8 Michels N, van de Wiele T, Fouhy F, et al. Gut microbiome patterns depending on children′s psychosocial stress: reports versus biomarkers[J]. Brain Behav Immun, 2019, 80: 751-762.
9 Siopi E, Chevalier G, Katsimpardi L, et al. Changes in gut microbiota by chronic stress impair the efficacy of fluoxetine[J]. Cell Rep, 2020, 30(11): 3682-3690.e6.
10 Sinopoli VM, Burton CL, Kronenberg S, et al. A review of the role of serotonin system genes in obsessive-compulsive disorder[J]. Neurosci Biobehav Rev, 2017, 80: 372-381.
11 Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases[J]. Am J Psychiatry, 1998, 155(2): 264-271.
12 Quagliariello A, Del Chierico F, Russo A, et al. Gut microbiota profiling and gut-brain crosstalk in children affected by pediatric acute-onset neuropsychiatric syndrome and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections[J]. Front Microbiol, 2018, 9: 675.
13 Turna J, Grosman Kaplan K, Anglin R, et al. The gut microbiome and inflammation in obsessive-compulsive disorder patients compared to age- and sex-matched controls: a pilot study[J]. Acta Psychiatr Scand, 2020, 142(4): 337-347.
14 Domènech L, Willis J, Alemany M, et al. Changes in the stool and oropharyngeal microbiome in obsessive-compulsive disorder[EB/OL]. medRxiv, 2020. DOI: 10.1101/2020.05.26.20113779.
15 Traina G. Mast cells in gut and brain and their potential role as an emerging therapeutic target for neural diseases[J]. Front Cell Neurosci, 2019, 13: 345.
16 Zhu SB, Jiang YF, Xu KL, et al. The progress of gut microbiome research related to brain disorders[J]. J Neuroinflammation, 2020, 17(1): 1-20.
17 Rivière A, Selak M, Lantin D, et al. Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut[J]. Front Microbiol, 2016, 7: 979.
18 Frodl T, O′Keane V. How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans[J]. Neurobiol Dis, 2013, 52: 24-37.
19 ?im?ek ?, Gen?o?lan S, Yüksel T, et al. Cortisol and brain-derived neurotrophic factor levels prior to treatment in children with obsessive-compulsive disorder[J]. J Clin Psychiatry, 2016, 77(7): e855-e859.
20 de Punder K, Pruimboom L. Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability[J]. Front Immunol, 2015, 6: 223.
21 Kelly JR, Kennedy PJ, Cryan JF, et al. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders[J]. Front Cell Neurosci, 2015, 9: 392.
22 Heim C, Newport DJ, Heit S, et al. Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood[J]. JAMA, 2000, 284(5): 592-597.
23 Ait-Belgnaoui A, Colom A, Braniste V, et al. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice[J]. Neurogastroenterol Motil, 2014, 26(4): 510-520.
24 Grados M, Prazak M, Saif A, et al. A review of animal models of obsessive-compulsive disorder: a focus on developmental, immune, endocrine and behavioral models[J]. Expert Opin Drug Discov, 2016, 11(1): 27-43.
25 Stuchlik A, Radostová D, Hatalova H, et al. Validity of quinpirole sensitization rat model of OCD: linking evidence from animal and clinical studies[J]. Front Behav Neurosci, 2016, 10: 209.
26 Jung TD, Jung PS, Raveendran L, et al. Changes in gut microbiota during development of compulsive checking and locomotor sensitization induced by chronic treatment with the dopamine agonist quinpirole[J]. Behav Pharmacol, 2018, 29(2 and 3-Spec Issue): 211-224.
27 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(2): 164-174.
28 Hirschtritt ME, Bloch MH, Mathews CA. Obsessive-compulsive disorder: advances in diagnosis and treatment[J]. JAMA, 2017, 317(13): 1358-1367.
29 Fülling C, Dinan TG, Cryan JF. Gut microbe to brain signaling: what happens in vagus…[J]. Neuron, 2019, 101(6): 998-1002.
30 Suarez AN, Hsu TM, Liu CM, et al. Gut vagal sensory signaling regulates hippocampus function through multi-order pathways[J]. Nat Commun, 2018, 9(1): 2181.
31 Lyte M, Li W, Opitz N, et al. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium[J]. Physiol Behav, 2006, 89(3): 350-357.
32 Bravo JA, Forsythe P, Chew MV, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve[J]. PNAS, 2011, 108(38): 16050-16055.
33 Sgritta M, Dooling SW, Buffington SA, et al. Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder[J]. Neuron, 2019, 101(2): 246-259. e6.
34 Jackson MA, Verdi S, Maxan ME, et al. Gut microbiota associations with common diseases and prescription medications in a population-based cohort[J]. Nat Commun, 2018, 9(1): 2655.
35 Sun LJ, Zhang HH, Cao Y, et al. Fluoxetine ameliorates dysbiosis in a depression model induced by chronic unpredicted mild stress in mice[J]. Int J Med Sci, 2019, 16(9): 1260-1270.
36 Fung TC, Vuong HE, Luna CDG, et al. Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut[J]. Nat Microbiol, 2019, 4(12): 2064-2073.
37 Lyte M, Daniels KM, Schmitz-Esser S. Fluoxetine-induced alteration of murine gut microbial community structure: evidence for a microbial endocrinology-based mechanism of action responsible for fluoxetine-induced side effects[J]. PeerJ, 2019, 7: e6199.
38 Farhood Z, Ong AA, Discolo CM. PANDAS: a systematic review of treatment options[J]. Int J Pediatr Otorhinolaryngol, 2016, 89: 149-153.
39 Esalatmanesh S, Abrishami Z, Zeinoddini A, et al. Minocycline combination therapy with fluvoxamine in moderate-to-severe obsessive-compulsive disorder: a placebo-controlled, double-blind, randomized trial[J]. Psychiatry Clin Neurosci, 2016, 70(11): 517-526.
40 Rodriguez CI, Bender J Jr, Marcus SM, et al. Minocycline augmentation of pharmacotherapy in obsessive-compulsive disorder: an open-label trial[J]. J Clin Psychiatry, 2010, 71(9): 1247-1249.
41 Kantak PA, Bobrow DN, Nyby JG. Obsessive-compulsive-like behaviors in house mice are attenuated by a probiotic (Lactobacillus rhamnosus GG)[J]. Behav Pharmacol, 2014, 25(1): 71-79.
42 Messaoudi M, Violle N, Bisson JF, et al. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers[J]. Gut Microbes, 2011, 2(4): 256-261.
Options
文章导航

/

〈 〉