基于微生物-肠-脑轴探讨神经递质在失眠中的研究进展

职业与健康 ›› 2026, Vol. 42 ›› Issue (21): 2996-3002.

基于微生物-肠-脑轴探讨神经递质在失眠中的研究进展

敖天娇¹^,², 姚娓¹^,²(), 刘惠珠¹^,², 孙静¹^,², 张雅铷¹^,², 曹怡婷¹^,²

¹ 大连医科大学附属第二医院，辽宁大连 116023
² 大连医科大学中西医结合学院/研究院，辽宁大连 116044

收稿日期:2025-11-03 修回日期:2025-12-23 出版日期:2026-11-01 发布日期:2026-09-04
通信作者: 姚娓，E-mail：411484335@qq.com
作者简介:敖天娇，女，在读硕士研究生，研究方向为中西医结合治疗内科疑难杂症。第一联系人：作者贡献
敖天娇负责文章的构思与设计、研究资料的收集与整理、论文撰写与修改；刘惠珠、孙静负责文献整理；张雅铷、曹怡婷负责核实数据；姚娓进行文章修订、审校，对文章整体负责、监督管理
基金资助:
第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]1号);“兴辽英才计划”医学名家项目(YXMJ-MZY-08);辽宁省自然科学基金面上项目(2022-MS-334)

Research progress on neurotransmitters in insomnia based on the microbiota-gut-brain axis

AO Tianjiao¹^,², YAO Wei¹^,²(), LIU Huizhu¹^,², SUN Jing¹^,², ZHANG Yaru¹^,², CAO Yiting¹^,²

¹ The Second Hospital of Dalian Medical University， Dalian， Liaoning 116023， China
² Institute of Integrative Traditional Chinese and Western Medicine， Dalian Medical University，Dalian， Liaoning 116044， China

Received:2025-11-03 Revised:2025-12-23 Online:2026-11-01 Published:2026-09-04
Contact: YAO Wei，E-mail：411484335@qq.com

摘要/Abstract

摘要：

失眠以频繁而持续的入睡困难或睡眠维持困难为特征，是临床最常见的睡眠障碍之一。定植在胃肠道中的微生物群具有调节中枢神经系统功能的能力，有研究发现，肠道微生物群和中枢神经系统之间存在双向通信，称为“微生物-肠-脑轴”，其与失眠的发生和发展密切相关。中枢系统神经递质参与介导睡眠-觉醒周期的调控，相关神经递质水平的微量变化对睡眠质量有着重要影响。本文综述了基于微生物-肠-脑轴的神经递质在失眠中的作用及研究进展，系统梳理并综合分析相关机制和未来治疗前景，为深入理解失眠的产生机制和有效治疗失眠提供新的视角。

关键词: 失眠, 肠道微生物, 神经递质, 睡眠, 微生物-肠-脑轴, 中枢神经系统

Abstract:

Insomnia is characterized by frequent and persistent difficulty in falling asleep or maintaining sleep，and is one of the most common sleep disorders in clinical practice. The microbiota residing in the gastrointestinal tract has the ability to regulate the function of the central nervous system. Studies have found that there is bidirectional communication between the gut microbiota and the central nervous system，known as the "microbiota-gut-brain axis"，and its changes are closely related to the occurrence and development of insomnia. Central nervous system neurotransmitters are involved in mediating the regulation of the sleep-wake cycle，and subtle changes in the levels of related neurotransmitters have a significant impact on sleep quality. This article reviews the role and research progress of neurotransmitters based on the microbiota-gut-brain axis in insomnia，systematically sorts out and comprehensively analyzes the related mechanisms and future treatment prospects，providing a new perspective for the in-depth understanding of the mechanism and effective treatment of insomnia.

Key words: Insomnia, Gut microbiota, Neurotransmitter, Sleep, Microbiota-gut-brain axis, Central nervous system

中图分类号:

R181.3+
7

敖天娇, 姚娓, 刘惠珠, 孙静, 张雅铷, 曹怡婷. 基于微生物-肠-脑轴探讨神经递质在失眠中的研究进展. [J]职业与健康, 2026, 42(21): 2996-3002.

AO Tianjiao, YAO Wei, LIU Huizhu, SUN Jing, ZHANG Yaru, CAO Yiting. Research progress on neurotransmitters in insomnia based on the microbiota-gut-brain axis. [J]OCCUPATION AND HEALTH, 2026, 42(21): 2996-3002.

参考文献 67

[1]	MORIN C M, BENCA R. Chronic insomnia[J]. Lancet, 2012, 379(9821):1129-1141.
[2]	中华医学会神经病学分会睡眠障碍学组. 中国成人失眠诊断与治疗指南(2023版)[J]. 中华神经科杂志, 2024, 57(6):560-584.
[3]	PERLIS M L, POSNER D, RIEMANN D, et al. Insomnia[J]. Lancet, 2022, 400(10357):1047-1060.
[4]	CAO X L, WANG S B, ZHONG B L, et al. The prevalence of insomnia in the general population in China:A meta-analysis[J]. PLoS One, 2017, 12(2):e0170772.
[5]	AGIRMAN G, HSIAO E Y. SnapShot:The microbiota-gut-brain axis[J]. Cell, 2021, 184(9):2524-2524.e1.
[6]	NAKHAL M M, YASSIN L K, ALYAQOUBI R, et al. The microbiota-gut-brain axis and neurological disorders:A comprehensive review[J]. Life, 2024, 14(10):1234.
[7]	LOH J S, MAK W Q, TAN L K S, et al. Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases[J]. Signal Transduction Targeted Ther, 2024, 9(1):37.
[8]	LIU L, ZHU J W, WU J L, et al. Insomnia and intestinal microbiota:A narrative review[J]. Sleep Breath, 2024, 29(1):10.
[9]	姜海洲, 韦姗姗, 胡金, 等. 睡眠-觉醒相关神经递质的研究进展[J]. 中国病理生理杂志, 2023, 39(7):1310-1317.
[10]	FÜLLING C, DINAN T G, CRYAN J F. Gut microbe to brain signaling:What happens in vagus...[J]. Neuron, 2019, 101(6):998-1002.
[11]	ADAK A, KHAN M R. An insight into gut microbiota and its functionalities[J]. Cell.Mol Life Sci, 2019, 76(3):473-493.
[12]	RAO M, GERSHON M D. The bowel and beyond:The enteric nervous system in neurological disorders[J]. Nat Rev Gastroenterol Hepatol, 2016, 13(9):517-528.
[13]	MARGOLIS K G, GERSHON M D, BOGUNOVIC M. Cellular organization of neuroimmune interactions in the gastrointestinal tract[J]. Trends Immunol, 2016, 37(7):487-501.
[14]	MARGOLIS K G, CRYAN J F, MAYER E A. The Microbiota-gut-brain axis:From motility to mood[J]. Gastroenterology, 2021, 160(5):1486-1501.
[15]	SANDHU K V, SHERWIN E, SCHELLEKENS H, et al. Feeding the microbiota-gut-brain axis:Diet,microbiome,and neuropsychiatry[J]. Transl Res, 2017, 179:223-244.
[16]	STRANDWITZ P. Neurotransmitter modulation by the gut microbiota[J]. Brain Res, 2018, 1693( Pt B):128-133.
[17]	JEWETT B E, SHARMA S. Physiology,GABA[EB/OL]. (2023-07-24)[2025-11-03]. https://www.ncbi.nlm.nih.gov/books/NBK513311/.
[18]	WONG C G T, BOTTIGLIERI T, SNEAD O C. GABA,gamma-hydroxybutyric acid,and neurological disease[J]. Ann Neurol, 2003, 54(Suppl 6):S3-S12.
[19]	JOHN J, WU M F, BOEHMER L N, et al. Cataplexy-active neurons in the hypothalamus:Implications for the role of histamine in sleep and waking behavior[J]. Neuron, 2004, 42(4):619-634.
[20]	SAPER C B, CHOU T C, SCAMMELL T E. The sleep switch:Hypothalamic control of sleep and wakefulness[J]. Trends Neurosci, 2001, 24(12):726-731.
[21]	CHARNAY Y, LÉGER L. Brain serotonergic circuitries[J]. Dialogues Clin Neurosci, 2010, 12(4):471-487.
[22]	DONG Y J, JIANG N H, ZHAN L H, et al. Soporific effect of modified suanzaoren decoction on mice models of insomnia by regulating orexin-a and HPA axis homeostasis[J]. Biomed Pharmacother, 2021, 143:112141.
[23]	陈燕, 许晓丽, 陈亚萍, 等. 半夏秫米汤对失眠大鼠下丘脑5-HT介导的cAMP/CREB/BDNF通路的影响[J]. 中药药理与临床, 2024, 40(10):10-14.
[24]	MAFFEI M E. 5-hydroxytryptophan(5-HTP):Natural occurrence,analysis,biosynthesis,biotechnology,physiology and toxicology[J]. Int J Mol Sci, 2020, 22(1):181.
[25]	MONTI J M. Serotonin control of sleep-wake behavior[J]. Sleep Med.Rev, 2011, 15(4):269-281.
[26]	PAQUELET G E, CARRION K, LACEFIELD C O, et al. Single-cell activity and network properties of dorsal raphe nucleus serotonin neurons during emotionally salient behaviors[J]. Neuron, 2022, 110(16):2664-2679.
[27]	张娅, 黄俊山, 张一帆, 等. 松郁安神方对失眠模型大鼠睡眠结构以及原代培养drn 5-ht能神经元兴奋性的影响[J]. 时珍国医国药, 2024, 35(5):1072-1076.
[28]	MONTI J M, JANTOS H. The roles of dopamine and serotonin,and of their receptors,in regulating sleep and waking[J]. Prog Brain Res, 2008, 172:625-646.
[29]	SULAMAN B A, WANG S, TYAN J, et al. Neuro-orchestration of sleep and wakefulness[J]. Nat Neurosci, 2023, 26(2):196-212.
[30]	MONTI J M, MONTI D. The involvement of dopamine in the modulation of sleep and waking[J]. Sleep Med Rev, 2007, 11(2):113-133.
[31]	HASEGAWA E, MIYASAKA A, SAKURAI K, et al. Rapid eye movement sleep is initiated by basolateral amygdala dopamine signaling in mice[J]. Science, 2022, 375(6584):994-1000.
[32]	DELBONO O, WANG Z M, MESSI M L. Brainstem noradrenergic neurons:Identifying a hub at the intersection of cognition,motility,and skeletal muscle regulation[J]. Acta Physiol(Oxf), 2022, 236(3):e13887.
[33]	CARTER M E, YIZHAR O, CHIKAHISA S, et al. Tuning arousal with optogenetic modulation of locus coeruleus neurons[J]. Nat.Neurosci, 2010, 13(12):1526-1533.
[34]	HOLST S C, LANDOLT H P. Sleep-wake neurochemistry[J]. Sleep Med Clin, 2022, 17(2):151-160.
[35]	SUN Y, ZHANG N, QU Y, et al. Shuangxia decoction alleviates p-chlorophenylalanine induced insomnia through the modification of serotonergic and immune system[J]. Metab.Brain Dis, 2020, 35(2):315-325.
[36]	BAO Y, ZHOU H, FU Y, et al. Zhumian granules improves PCPA-induced insomnia by regulating the expression level of neurotransmitters and reducing neuronal apoptosis[J]. J Ethnopharmacol, 2024, 327:118048.
[37]	JOHNSON K V A, FOSTER K R. Why does the microbiome affect behaviour?[J]. Nat Rev Microbiol, 2018, 16(10):647-655.
[38]	汪铮, 田培郡, 朱然, 等. 基于肠道类器官解析益生菌调节肠嗜铬细胞合成5-ht的效应物质[J]. 食品与发酵工业, 2023, 49(19):75-82.
[39]	ZHANG T, WANG W, LI J, et al. Free fatty acid receptor 4 modulates dietary sugar preference via the gut microbiota[J]. Nat Microbiol, 2025, 10(2):348-361.
[40]	WANG Z, WANG Z, LU T, et al. Gut microbiota regulate insomnia-like behaviors via gut-brain metabolic axis[J]. Mol Psychiatry, 2025, 30(6):2597-2611.
[41]	SEONG H J, BAEK Y, LEE S, et al. Gut microbiome and metabolic pathways linked to sleep quality[J]. Front Microbiol, 2024, 15:1418773.
[42]	PAN M, QIAN C, HUO S, et al. Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via akkermansia muciniphila[J]. Gut Microbes, 2025, 17(1):2447834.
[43]	BULL-LARSEN S, MOHAJERI M H. The potential influence of the bacterial microbiome on the development and progression of ADHD[J]. Nutrients, 2019, 11(11):2805.
[44]	SUGANYA K, KOO B S. Gut-brain axis:Role of gut microbiota on neurological disorders and how probiotics/prebiotics beneficially modulate microbial and immune pathways to improve brain functions[J]. Int J Mol Sci, 2020, 21(20):7551.
[45]	GABRIEL-SEGARD T, RONTARD J, MINY L, et al. Proof-of-concept human organ-on-chip study:First step of platform to assess neuro-immunological communication involved in inflammatory bowel diseases[J]. Int J Mol Sci, 2023, 24(13):10568.
[46]	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 U.S.A, 2011, 108(38):16050-16055.
[47]	LANG W, LI X, WANG Y, et al. Sodium propionate improves cognitive and memory function in mouse models of alzheimer’s disease[J]. Neuro Sci Lett, 2022, 791:136887.
[48]	QIAN X, LI Q, ZHU H, et al. Bifidobacteria with indole-3-lactic acid-producing capacity exhibit psychobiotic potential via reducing neuroinflammation[J]. Cell Rep Med, 2024, 5(11):101798.
[49]	LI C, WANG L, XIE W, et al. TGR5 deficiency in excitatory neurons ameliorates alzheimer's pathology by regulating APP processing[J]. Sci Adv, 2024, 10(26):eado1855.
[50]	HUANG F, PARIANTE C M, BORSINI A. From dried bear bile to molecular investigation:A systematic review of the effect of bile acids on cell apoptosis,oxidative stress and inflammation in the brain,across pre-clinical models of neurological,neurodegenerative and neuropsychiatric disorders[J]. Brain,Behav,Immun, 2022, 99:132-146.
[51]	O’DONNELL M P, FOX B W, CHAO P H, et al. A neurotransmitter produced by gut bacteria modulates host sensory behaviour[J]. Nature, 2020, 583(7816):415-420.
[52]	WANG X, WANG Z, CAO J, et al. Gut microbiota-derived metabolites mediate the neuroprotective effect of melatonin in cognitive impairment induced by sleep deprivation[J]. Microbiome, 2023, 11(1):17.
[53]	SHIMIZU Y, YAMAMURA R, YOKOI Y, et al. Shorter sleep time relates to lower human defensin 5 secretion and compositional disturbance of the intestinal microbiota accompanied by decreased short-chain fatty acid production[J]. Gut Microbes, 2023, 15(1):2190306.
[54]	XIE F, FENG Z, XU B. Metabolic characteristics of gut microbiota and insomnia:Evidence from a mendelian randomization analysis[J]. Nutrients, 2024, 16(17):2943.
[55]	RAMADAN Y N, ALQIFARI S F, ALSHEHRI K, et al. Microbiome gut-brain-axis:Impact on brain development and mental health[J]. Mol Neurobiol, 2025, 62:1-14.
[56]	GRECO M A, SHIROMANI P J. Hypocretin receptor protein and mRNA expression in the dorsolateral pons of rats[J]. Brain Res.Mol Brain Res, 2001, 88(1-2):176-182.
[57]	RIEMANN D, SPIEGELHALDER K, FEIGE B, et al. The hyperarousal model of insomnia:A review of the concept and its evidence[J]. Sleep Med.Rev, 2010, 14(1):19-31.
[58]	LIU T, FEENSTRA K A, HERINGA J, et al. Influence of gut microbiota on mental health via neurotransmitters:A review[J]. JAIMS, 2020, 1(1-2):1-14.
[59]	JIA M, FAN Y, MA Q, et al. Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder[J]. Transl.Psychiatry, 2024, 14(1):503.
[60]	FARAJI N, PAYAMI B, EBADPOUR N, et al. Vagus nerve stimulation and gut microbiota interactions:A novel therapeutic avenue for neuropsychiatric disorders[J]. NeuroSci Biobehav Rev, 2025, 169:105990.
[61]	TANG M, SONG X, ZHONG W, et al. Dietary fiber ameliorates sleep disturbance connected to the gut-brain axis[J]. Food Funct, 2022, 13(23):12011-12020.
[62]	SUTANTO C N, LOH W W, KIM J E. The impact of tryptophan supplementation on sleep quality:A systematic review,meta-analysis,and meta-regression[J]. Nutr Rev, 2022, 80(2):306-316.
[63]	BRAVO R, MATITO S, CUBERO J, et al. Tryptophan-enriched cereal intake improves nocturnal sleep,melatonin,serotonin,and total antioxidant capacity levels and mood in elderly humans[J]. Age(Dordrecht,Neth.), 2013, 35(4):1277-1285.
[64]	LIN Z, JIANG T, CHEN M, et al. Gut microbiota and sleep:Interaction mechanisms and therapeutic prospects[J]. Open Life Sci, 2024, 19(1):20220910.
[65]	CHINNA MEYYAPPAN A, FORTH E, WALLACE C J K, et al. Effect of fecal microbiota transplant on symptoms of psychiatric disorders:A systematic review[J]. BMC Psychiatry, 2020, 20(1):299.
[66]	MAO Q, ZHANG H, ZHANG Z, et al. Co-decoction of lilii bulbus and radix rehmannia recens and its key bioactive ingredient verbascoside inhibit neuroinflammation and intestinal permeability associated with chronic stress-induced depression via the gut microbiota-brain axis[J]. Phytomedicine, 2024, 129:155510.
[67]	余婷婷, 刘小路. 归脾汤化裁合酒石酸唑吡坦片治疗心脾两虚型不寐病疗效研究及对神经递质的影响[J]. 中国典型病例大全, 2025:1-5.