基于肠道菌群探讨针刺干预CID-MCI的机制研究进展
Advances in the Mechanisms of Acupuncture Intervention for CID-MCI: Insights from the Gut Microbiota
DOI: 10.12677/tcm.2026.1511629, PDF,    科研立项经费支持
作者: 沈 怡：成都中医药大学针灸推拿学院，四川 成都；侯天舒*：成都市中西医结合医院治未病中心，四川 成都
关键词: 针刺；慢性失眠；轻度认知功能障碍；肠道菌群；肠脑轴；Acupuncture； Chronic Insomnia； Mild Cognitive Impairment； Gut Microbiota； Gut-Brain Axis
摘要: 慢性失眠障碍(chronic insomnia disorder, CID)和轻度认知功能障碍(mild cognitive impairment, MCI)是老龄化背景下常见的神经精神疾病。两者在病理生理过程中存在明显的相互影响关系。长期睡眠障碍不仅会损害注意力、执行功能及记忆能力，还可能促进MCI向阿尔茨海默病进展。近年来，肠道菌群及其介导的肠道菌群–肠–脑轴(microbiota-gut-brain axis, MGBA)被认为是连接CID与MCI的重要生物学基础。肠道菌群可通过短链脂肪酸、神经递质、免疫炎症反应及下丘脑–垂体–肾上腺(HPA)轴等途径参与睡眠与认知功能调控。研究表明，针刺能够改善患者睡眠质量及认知功能，其机制可能与调节肠道菌群结构、增强肠黏膜屏障完整性、抑制神经炎症、调节5-羟色胺及γ-氨基丁酸等神经递质水平，以及改善迷走神经功能有关。现基于MGBA理论，对针刺干预CID-MCI的潜在机制进行综述，以期为相关机制研究及临床干预提供参考。
Abstract: Chronic insomnia disorder (CID) and mild cognitive impairment (MCI) are prevalent neuropsychiatric disorders in the aging population and exhibit substantial pathophysiological interplay. Persistent sleep disturbances not only impair attention, executive function, and memory performance, but may also accelerate the progression from MCI to Alzheimer’s disease (AD). In recent years, the gut microbiota and the microbiota-gut-brain axis (MGBA) have increasingly been recognized as important biological links between cancer-induced distress (CID) and mild cognitive impairment (MCI). The gut microbiota participate in the regulation of sleep and cognitive function through multiple pathways, including short-chain fatty acid (SCFA) production, neurotransmitter modulation, immune-inflammatory responses, and regulation of the hypothalamic-pituitary adrenal (HPA) axis. Accumulating evidence suggests that acupuncture can improve sleep quality and cognitive function, potentially through modulating gut microbiota composition, enhancing intestinal mucosal barrier integrity, attenuating neuroinflammation, regulating neurotransmitter levels, particularly 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA), and improving vagal nerve function. Based on the MGBA framework, this review systematically summarizes the potential mechanisms underlying the effects of acupuncture on CID-MCI, with the aim of providing scientific reference for further mechanistic investigations and clinical intervention strategies.
文章引用：沈怡, 侯天舒. 基于肠道菌群探讨针刺干预CID-MCI的机制研究进展[J]. 中医学, 2026, 15(11): 108-115. https://doi.org/10.12677/tcm.2026.1511629

参考文献

[1] Ferini‐Strambi, L., Auer, R., Bjorvatn, B., Castronovo, V., Franco, O., Gabutti, L., et al. (2021) Insomnia Disorder: Clinical and Research Challenges for the 21st Century. European Journal of Neurology, 28, 2156-2167.
https://doi.org/10.1111/ene.14784
[2] Pang, R., Guo, R., Wu, X., Hu, F., Liu, M., Zhang, L., et al. (2018) Altered Regional Homogeneity in Chronic Insomnia Disorder with or without Cognitive Impairment. American Journal of Neuroradiology, 39, 742-747.
https://doi.org/10.3174/ajnr.a5587
[3] Peter-Derex, L., Yammine, P., Bastuji, H. and Croisile, B. (2015) Sleep and Alzheimer’s Disease. Sleep Medicine Reviews, 19, 29-38.
https://doi.org/10.1016/j.smrv.2014.03.007
[4] 郑建星, 赵梦晴, 骆云晨, 等. 肠道菌群关键代谢物对阿尔茨海默病进程的研究进展[J]. 微生物学报, 2026, 66(7): 3139-3149.
[5] Morais, L.H., Schreiber, H.L. and Mazmanian, S.K. (2021) The Gut Microbiota-Brain Axis in Behaviour and Brain Disorders. Nature Reviews Microbiology, 19, 241-255.
https://doi.org/10.1038/s41579-020-00460-0
[6] Li, Y., Zhang, B., Zhou, Y., Wang, D., Liu, X., Li, L., et al. (2020) Gut Microbiota Changes and Their Relationship with Inflammation in Patients with Acute and Chronic Insomnia. Nature and Science of Sleep, 12, 895-905.
https://doi.org/10.2147/nss.s271927
[7] Libriani, S., Facchinetti, G., Marti, F., Tolentino Diaz, M.Y. and Sandri, E. (2026) The Association between Gut Microbiota and Cognitive Decline: A Systematic Review of the Literature. Nutrition Research, 147, 16-31.
https://doi.org/10.1016/j.nutres.2026.01.003
[8] Wang, Y., Du, W., Hu, X., Yu, X., Guo, C., Jin, X., et al. (2023) Targeting the Blood-Brain Barrier to Delay Aging-Accompanied Neurological Diseases by Modulating Gut Microbiota, Circadian Rhythms, and Their Interplays. Acta Pharmaceutica Sinica B, 13, 4667-4687.
https://doi.org/10.1016/j.apsb.2023.08.009
[9] 尹丽英, 冉然, 刘玉红, 等. 血清GABA、5-HT水平与慢性失眠患者睡眠质量和认知功能的关系[J]. 检验医学与临床, 2025, 22(17): 2362-2367.
[10] Yano, J., Yu, K., Donaldson, G., Shastri, G., Ann, P., Ma, L., et al. (2015) Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Cell, 161, 264-276.
https://doi.org/10.1016/j.cell.2015.02.047
[11] 陈凤, 王龙娟, 李贞贞, 等. 大鼠肠道菌群变化影响其大脑海马脑源性神经营养因子的表达[J]. 中国微生态学杂志, 2015, 27(1): 10-13.
[12] Horn, J., Mayer, D.E., Chen, S. and Mayer, E.A. (2022) Role of Diet and Its Effects on the Gut Microbiome in the Pathophysiology of Mental Disorders. Translational Psychiatry, 12, Article No. 164.
https://doi.org/10.1038/s41398-022-01922-0
[13] Mayer, G., Frohnhofen, H., Jokisch, M., Hermann, D.M. and Gronewold, J. (2024) Associations of Sleep Disorders with All-Cause MCI/Dementia and Different Types of Dementia—Clinical Evidence, Potential Pathomechanisms and Treatment Options: A Narrative Review. Frontiers in Neuroscience, 18, Article ID: 1372326.
https://doi.org/10.3389/fnins.2024.1372326
[14] Longo, S., Rizza, S. and Federici, M. (2023) Microbiota-Gut-Brain Axis: Relationships among the Vagus Nerve, Gut Microbiota, Obesity, and Diabetes. Acta Diabetologica, 60, 1007-1017.
https://doi.org/10.1007/s00592-023-02088-x
[15] Varpaei, H.A., Robbins, L.B., Reeves, M.J., Deka, P., Mowbray, F.I. and Quan, S.F. (2026) Gut Microbiota, Sleep Quality, and Cognitive Function in Adults: A Systematic Review. Sleep Medicine, 141, Article ID: 108834.
https://doi.org/10.1016/j.sleep.2026.108834
[16] Wang, T., Li, Z., Ma, T., Zhu, F., Yang, B., Kim, S., et al. (2024) Brain Function Assessment of Acupuncture for Chronic Insomnia Disorder with Mild Cognitive Dysfunction Based on fNIRS: Protocol for a Randomized Controlled Trial. Frontiers in Neurology, 15, Article ID: 1403785.
https://doi.org/10.3389/fneur.2024.1403785
[17] Yu, C., Li, M., Shen, F., Gao, S., Wang, J., He, C., et al. (2025) Electroacupuncture Alleviates Cognitive Impairments in APP/PS1 Mice via Gastric Vagal Afferent-Mediated Activation of the Nucleus Tractus Solitarius-Locus Coeruleus Noradrenergic Circuit. Chinese Medicine, 20, Article No. 188.
https://doi.org/10.1186/s13020-025-01230-x
[18] 宋晶. 电针四神聪改善脑梗死患者睡眠结构、认知功能的临床研究及机制探讨[D]: [博士学位论文]. 哈尔滨: 黑龙江中医药大学, 2018.
[19] 王海琴, 谢西梅. 针刺对失眠患者认知功能量表影响的研究[C]//中国针灸学会. 2024中国针灸学会年会论文集. 2024: 515-518.
[20] Hong, J., Chen, J., Kan, J., Liu, M. and Yang, D. (2020) Effects of Acupuncture Treatment in Reducing Sleep Disorder and Gut Microbiota Alterations in PCPA‐Induced Insomnia Mice. Evidence-Based Complementary and Alternative Medicine, 2020, Article ID: 3626120.
https://doi.org/10.1155/2020/3626120
[21] 蒋鹏, 胡芬, 林冕, 等. 针刺治疗轻度认知功能障碍的临床疗效及对肠道菌群的影响[J]. 中国针灸, 2025, 45(7): 903-910.
[22] Jiang, J., Liu, H., Wang, Z., Tian, H., Wang, S., Yang, J., et al. (2021) Electroacupuncture Could Balance the Gut Microbiota and Improve the Learning and Memory Abilities of Alzheimer’s Disease Animal Model. PLOS ONE, 16, e0259530.
https://doi.org/10.1371/journal.pone.0259530
[23] Kang, J., Chen, J., Li, P., Zhao, S., Jing, F., Xie, J., et al. (2025) Study on the Relationship between Insomnia Disorder, PET/CT, and Gut Microbiota in Patients with Alzheimer’s Disease. Frontiers in Neurology, 16, Article ID: 1669835.
https://doi.org/10.3389/fneur.2025.1669835
[24] He, C., Huang, Z.S., Yu, C.C., et al. (2021) Preventive Electroacupuncture Ameliorates D-Galactose-Induced Alzheimer’s Disease-Like Inflammation and Memory Deficits, Probably via Modulating the Microbiota-Gut-Brain Axis. Iranian Journal of Basic Medical Sciences, 24, 341-348.
[25] Yu, H.J., Jing, C., Xiao, N., et al. (2020) Structural Difference Analysis of Adult’s Intestinal Flora Basing on the 16S rDNA Gene Sequencing Technology. European Review for Medical and Pharmacological Sciences, 24, 12983-12992.
[26] Dowling, L.R., Strazzari, M.R., Keely, S. and Kaiko, G.E. (2022) Enteric Nervous System and Intestinal Epithelial Regulation of the Gut-Brain Axis. Journal of Allergy and Clinical Immunology, 150, 513-522.
https://doi.org/10.1016/j.jaci.2022.07.015
[27] Mann, E.R., Lam, Y.K. and Uhlig, H.H. (2024) Short-Chain Fatty Acids: Linking Diet, the Microbiome and Immunity. Nature Reviews Immunology, 24, 577-595.
https://doi.org/10.1038/s41577-024-01014-8
[28] Matt, S.M., Allen, J.M., Lawson, M.A., Mailing, L.J., Woods, J.A. and Johnson, R.W. (2018) Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated with Aging in Mice. Frontiers in Immunology, 9, Article No. 1832.
https://doi.org/10.3389/fimmu.2018.01832
[29] Wang, J., Pan, Y., Cao, Y., Wang, C., Jiang, W., Zhai, W., et al. (2020) Loganin Alleviates LPS‐Activated Intestinal Epithelial Inflammation by Regulating TLR4/NF-κB and JAK/STAT3 Signaling Pathways. The Kaohsiung Journal of Medical Sciences, 36, 257-264.
https://doi.org/10.1002/kjm2.12160
[30] Dong, Z.Q., Zhu, J., Lu, D.Z., et al. (2018) Effect of Electroacupuncture in “Zusanli” and “Kunlun” Acupoints on TLR4 Signaling Pathway of Adjuvant Arthritis Rats. American Journal of Therapeutics, 25, e314-e319.
[31] Jang, J.H., Yeom, M.J., Ahn, S., et al. (2020) Acupuncture Inhibits Neuroinflammation and Gut Microbial Dysbiosis in a Mouse Model of Parkinson’s Disease. Brain, Behavior, and Immunity, 89, 641-655.
[32] 李瑒. 电针通过NLRP3/Caspase-1细胞焦亡信号通路改善SAMP8小鼠轻度认知障碍的作用机制研究[D]: [硕士学位论文]. 哈尔滨: 黑龙江中医药大学, 2022.
[33] Wang, W., Wang, Y., Guo, Q., Li, H., Wang, Z., Li, J., et al. (2022) Valerian Essential Oil for Treating Insomnia via the Serotonergic Synapse Pathway. Frontiers in Nutrition, 9, Article ID: 927434.
https://doi.org/10.3389/fnut.2022.927434
[34] Yu, Y., Li, J., He, X., Lai, Z., Hao, R., Qi, Y., et al. (2022) 5-HT3A Receptors Maintain Hippocampal LTP in a CB1 and GABAA Receptor‐ Dependent Manner for Spatial Memory. British Journal of Pharmacology, 179, 2969-2985.
https://doi.org/10.1111/bph.15793
[35] 廖凌鑫, 刘薪雨, 李仲文, 等. 神门、三阴交穴位配伍对不同主症失眠症患者临床症状和血清5-HT、GABA的影响[J]. 时珍国医国药, 2024, 35(5): 1164-1168.
[36] Wang, X., Yan, L., Zhang, X., Liu, X. and Yang, B. (2025) Electroacupuncture as Adjunctive Therapy for Insomnia via Targeting the GABAergic Microbiota-Gut-Brain Axis: A Mini Review. Frontiers in Psychiatry, 16, Article ID: 1613408.
https://doi.org/10.3389/fpsyt.2025.1613408
[37] 陈潞婷, 高杏, 魏巍. 电针调节GABAa受体表达改善脑缺血大鼠认知功能障碍的研究[J]. 时珍国医国药, 2025, 36(3): 576-580.
[38] 杨淑荃, 范德辉, 罗孟西, 等. 腹针对轻中度阿尔茨海默病患者认知功能及血清5-HT、BDNF、IGF-1的影响[J]. 上海针灸杂志, 2023, 42(5): 485-490.
[39] 冯旭, 陈路, 王富春. 近五年针刺治疗慢性失眠障碍的作用机制研究进展[J]. 环球中医药, 2026, 19(1): 168-174.
[40] Tofani, G.S.S., Leigh, S., Gheorghe, C.E., Bastiaanssen, T.F.S., Wilmes, L., Sen, P., et al. (2025) Gut Microbiota Regulates Stress Responsivity via the Circadian System. Cell Metabolism, 37, 138-153.e5.
https://doi.org/10.1016/j.cmet.2024.10.003
[41] Cryan, J.F. and Dinan, T.G. (2012) Mind-Altering Microorganisms: The Impact of the Gut Microbiota on Brain and Behaviour. Nature Reviews Neuroscience, 13, 701-712.
https://doi.org/10.1038/nrn3346
[42] Gershon, M.D. and Margolis, K.G. (2021) The Gut, Its Microbiome, and the Brain: Connections and Communications. Journal of Clinical Investigation, 131, e143768.
https://doi.org/10.1172/jci143768
[43] Zhang, F., Zhang, X., Peng, Q. and Tang, L. (2023) Electroacupuncture of the Cymba Concha Alleviates P-Chlorophenylalanine-Induced Insomnia in Mice. Acupuncture in Medicine, 41, 345-353.
https://doi.org/10.1177/09645284231160193