肠道菌群与阻塞性睡眠呼吸暂停综合征合并认知功能障碍的研究进展

doi:10.3760/cma.j.cn441417-20240730-01010

摘要/Abstract

摘要：

阻塞性睡眠呼吸暂停综合征（OSAS）是以间歇性低氧和睡眠碎片化为主要表现的一类疾病，严重影响患者的睡眠质量。OSAS易合并认知功能障碍，主要表现在记忆力、注意力、执行力等方面。目前认为，OSAS患者肠道内菌群稳态遭到破坏可能与认知功能障碍有关。本文就肠道菌群与OSAS合并认知功能障碍的相关研究进行综述。

关键词:

肠道菌群, 阻塞性睡眠呼吸暂停综合征, 认知功能障碍, 进展

Abstract:

Obstructive sleep apnea syndrome (OSAS) is a class of diseases characterized by intermittent hypoxia and sleep fragmentation, which seriously affect the patients' sleep quality, and then combine with some cognitive dysfunction, including memory attention and executive function decline. At present, the mechanism of cognitive impairment in OSAS patients is not clear. Studies have shown that the homeostasis of gut microbiota in OSAS patients is disrupted, and the reduction of some flora destroys the internal environment of gut microbiota, leading to cognitive impairment. The present study reviews the research progress of OSAS combined with cognitive dysfunction based on gut microbiota.

Key words:

Gut microbiota, Obstructive sleep apnea syndrome, Cognitive impairment, Progress

吴京霖卢曼路李明珍刘璐于燕潘磊.

肠道菌群与阻塞性睡眠呼吸暂停综合征合并认知功能障碍的研究进展 [J]. 国际医药卫生导报, 2025, 31(1): 47-50.

Wu Jinglin, Lu Manlu, Li Mingzhen, Liu Lu, Yu Yan, Pan Lei.

Recent advances of the research between gut microbiota and obstructive sleep apnea syndrome combined with cognitive impairment [J]. International Medicine and Health Guidance News, 2025, 31(1): 47-50.

参考文献

[1] Qureshi A, Ballard RD. Obstructive sleep apnea[J]. J Allergy Clin Immunol, 2003, 112(4): 643-651, 652. DOI: 10.1016/j.jaci.2003.08.031.
[2] Ko CY, Liu QQ, Su HZ, et al. Gut microbiota in obstructive sleep apnea-hypopnea syndrome: disease-related dysbiosis and metabolic comorbidities[J]. Clin Sci (Lond), 2019, 133(7): 905-917. DOI: 10.1042/CS20180891.
[3] Li D, Xu N, Hou Y, et al. Abnormal lipid droplets accumulation induced cognitive deficits in obstructive sleep apnea syndrome mice via JNK/SREBP/ACC pathway but not through PDP1/PDC pathway[J]. Mol Med, 2022, 28(1): 3. DOI: 10.1186/s10020-021-00427-8.
[4] Adak A, Khan MR. An insight into gut microbiota and its functionalities[J]. Cell Mol Life Sci, 2019, 76(3): 473-493. DOI: 10.1007/s00018-018-2943-4.
[5] Kuziel GA, Rakoff-Nahoum S. The gut microbiome[J]. Curr Biol, 2022, 32(6): R257-R264. DOI: 10.1016/j.cub.2022. 02.023.
[6] Lv R, Liu X, Zhang Y, et al. Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome[J]. Signal Transduct Target Ther, 2023, 8(1): 218. DOI: 10.1038/s41392-023-01496-3.
[7] Wei Y, Huang L, Liu C, et al. Causal relationship between gut microbiota and obstructive sleep apnea [J]. Arch Gerontol Geriatr, 2023, 113: 105052. DOI: 10.1016/j.archger.2023.105052.
[8] Badran M, Khalyfa A, Ericsson AC, et al. Gut microbiota mediate vascular dysfunction in a murine model of sleep apnoea: effect of probiotics [J]. Eur Respir J, 2023, 61(1):2200002.. DOI: 10.1183/13993003.00002-2022.
[9] Zhang C, Chen F, Shen Y, et al. Sleep apnea is associated with the increase of certain genera of ruminococcaceae and lachnospiraceae in the gut microbiome of hypertensive patients [J]. Expert Rev Respir Med, 2022, 16(11-12): 1247-1256. DOI: 10.1080/17476348.2022. 2147509.
[10] Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication [J]. Front Endocrinol (Lausanne), 2020, 11: 25. DOI: 10.3389/fendo.2020.00025.
[11] Liu W, Du Q, Zhang H, et al. The gut microbiome and obstructive sleep apnea syndrome in children [J]. Sleep Med, 2022, 100: 462-471. DOI: 10.1016/j.sleep.2022. 09.022.
[12] Zhang Y, Luo H, Niu Y, et al. Chronic intermittent hypoxia induces gut microbial dysbiosis and infers metabolic dysfunction in mice [J]. Sleep Med, 2022, 91: 84-92. DOI: 10.1016/j.sleep.2022.02.003.
[13] Wang F, Liu Q, Wu H, et al. The dysbiosis gut microbiota induces the alternation of metabolism and imbalance of Th17/Treg in OSA patients [J]. Arch Microbiol, 2022, 204(4): 217. DOI: 10.1007/s00203-022-02825-w.
[14] 王利娟,杨冲,窦占军,等. 不同严重程度阻塞性睡眠呼吸暂停低通气患者肠道菌群特征初步分析[J]. 中华结核和呼吸杂志,2021,44(6):543-549. DOI:10.3760/cma.j.cn112147- 20201009-01027.
[15] Ganesh BP, Nelson JW, Eskew JR, et al. Prebiotics, probiotics, and acetate supplementation prevent hypertension in a model of obstructive sleep apnea [J]. Hypertension, 2018, 72(5): 1141-1150. DOI: 10.1161/hypertensionaha.118.11695.
[16] Moreno-Indias I, Torres M, Sanchez-Alcoholado L, et al. Normoxic recovery mimicking treatment of sleep apnea does not reverse intermittent hypoxia-induced bacterial dysbiosis and low-grade endotoxemia in mice [J]. Sleep, 2016, 39(10): 1891-1897. DOI: 10.5665/sleep.6176.
[17] Barrio C, Arias-Sánchez S, Martín-Monzón I. The gut microbiota-brain axis, psychobiotics and its influence on brain and behaviour: a systematic review [J]. Psychoneuroendocrinology, 2022, 137: 105640. DOI: 10.1016/j.psyneuen.2021.105640.
[18] Dumitrescu L, Popescu-Olaru I, Cozma L, et al. Oxidative stress and the microbiota-gut-brain axis [J]. Oxid Med Cell Longev, 2018, 2018: 2406594. DOI: 10.1155/2018/2406594.
[19] Patel A, Chong DJ. Obstructive sleep apnea [J]. Clin Geriatr Med, 2021, 37(3): 457-467. DOI: 10.1016/j.cger.2021. 04.007.
[20] 卢曼路,朱继伟,丁红红,等. 阻塞性睡眠呼吸暂停低通气综合征与肠道菌群关系的研究进展[J]. 国际医药卫生导报,2024,30(10):1585-1589. DOI:10.3760/cma.j.issn.1007- 1245.2024.10.001.
[21] Nagpal R, Neth BJ, Wang S, et al. Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment [J]. EBioMedicine, 2019, 47: 529-542. DOI: 10.1016/j.ebiom.2019.08.032.
[22] Hung CC, Chang CC, Huang CW, et al. Gut microbiota in patients with Alzheimer's disease spectrum: a systematic review and meta-analysis [J]. Aging (Albany NY), 2022, 14(1): 477-496. DOI: 10.18632/aging.203826.
[23] Lee J, Venna VR, Durgan DJ, et al. Young versus aged microbiota transplants to germ-free mice: increased short-chain fatty acids and improved cognitive performance [J]. Gut Microbes, 2020, 12(1): 1-14. DOI: 10.1080/19490976.2020.1814107.
[24] Prévot T, Sibille E. Altered GABA-mediated information processing and cognitive dysfunctions in depression and other brain disorders [J]. Mol Psychiatry, 2021, 26(1): 151-167. DOI: 10.1038/s41380-020-0727-3.
[25] Wang X, Sun G, Feng T, et al. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression [J]. Cell Res, 2019, 29(10): 787-803. DOI: 10.1038/s41422-019- 0216-x.
[26] 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. DOI: 10.1186/s40168-022-01452-3.
[27] Morley JE. An overview of cognitive impairment [J]. Clin Geriatr Med, 2018, 34(4): 505-513. DOI: 10.1016/j.cger.2018.06.003.
[28] Lu X, Xue Z, Qian Y, et al. Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats [J]. Front Cell Infect Microbiol, 2022, 12: 945851. DOI: 10.3389/fcimb.2022.945851.
[29] Wu L, Han Y, Zheng Z, et al. Altered gut microbial metabolites in amnestic mild cognitive impairment and alzheimer's disease: signals in host–microbe interplay [J]. Nutrients, 2021, 13(1):228. DOI: 10.3390/nu13010228.
[30] Teng Y, Mu J, Xu F, et al. Gut bacterial isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death [J]. Cell Host Microbe, 2022, 30(7): 944-960, e8. DOI: 10.1016/j.chom.2022.05.005.
[31] Bairamian D, Sha S, Rolhion N, et al. Microbiota in neuroinflammation and synaptic dysfunction: a focus on alzheimer's disease [J]. Mol Neurodegener, 2022, 17(1): 19. DOI: 10.1186/s13024-022-00522-2.
[32] Li D, Ke Y, Zhan R, et al. Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice [J]. Aging Cell, 2018, 17(4):e12768. DOI: 10.1111/acel.12768.
[33] Quigley EMM. Microbiota-brain-gut axis and neurodegenerative diseases [J]. Curr Neurol Neurosci Rep, 2017, 17(12): 94. DOI: 10.1007/s11910-017-0802-6.
[34] Anand N, Gorantla VR, Chidambaram SB. The role of gut dysbiosis in the pathophysiology of neuropsychiatric disorders [J]. Cells, 2022, 12(1):54. DOI: 10.3390/cells12010054.
[35] Wang Z, Chen WH, Li SX, et al. Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation [J]. Mol Psychiatry, 2021, 26(11): 6277-6292. DOI: 10.1038/s41380-021-01113-1.
[36] Shi H, Ge X, Ma X, et al. A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites [J]. Microbiome, 2021, 9(1): 223. DOI: 10.1186/s40168-021-01172-0.
[37] Bowers M, Liang T, Gonzalez-Bohorquez D, et al. FASN-dependent lipid metabolism links neurogenic stem/progenitor cell activity to learning and memory deficits [J]. Cell Stem Cell, 2020, 27(1): 98-109, e11. DOI: 10.1016/j.stem.2020.04.002.
[38] Najmabadi H, Hu H, Garshasbi M, et al. Deep sequencing reveals 50 novel genes for recessive cognitive disorders [J]. Nature, 2011, 478(7367): 57-63. DOI: 10.1038/nature10423.
[39] Erny D, Hrabě de Angelis AL, Jaitin D, et al. Host microbiota constantly control maturation and function of microglia in the CNS [J]. Nat Neurosci, 2015, 18(7): 965-977. DOI: 10.1038/nn.4030.
[40] Lago-Baldaia I, Fernandes VM, Ackerman SD. More than mortar: glia as architects of nervous system development and disease [J]. Front Cell Dev Biol, 2020, 8:611269. DOI: 10.3389/fcell.2020.611269.
[41] Roh JS, Sohn DH. Damage-associated molecular patterns in inflammatory diseases [J]. Immune Netw, 2018, 18(4):e27. DOI: 10.4110/in.2018.18.e27.
[42] Liu F, Liu T-W, Kang J. The role of NF-κB-mediated JNK pathway in cognitive impairment in a rat model of sleep apnea [J]. J Thorac Dis, 2018, 10(12): 6921-6931. DOI: 10.21037/jtd.2018.12.05.