肠道微生物及其代谢物与脑血管疾病关系的研究进展
Research Progress on the Relationship between Gut Microbiota and Its Metabolites and Cerebrovascular Diseases
DOI: 10.12677/acm.2025.15123635, PDF,    科研立项经费支持
作者: 叶铖龙:绍兴文理学院医学院,浙江 绍兴;王建莉*:绍兴市人民医院神经外科,浙江 绍兴
关键词: 脑血管疾病脑出血脑卒中肠道微生物肠道菌群失调微生物代谢物Cerebrovascular Disease Intracerebral Hemorrhage Stroke Gut Microbiota Gut Dysbiosis Microbial Metabolites
摘要: 脑血管疾病的发病机制尚未完全明确,肠道菌群失调可能在其发展过程中发挥作用。本文通过综述相关研究发现,高血压患者肠道菌群多样性显著降低,且高血压患者的肠道菌群可导致无菌小鼠血压升高。以普雷沃菌(Prevotella)和克雷伯菌(Klebsiella)为代表的促炎菌群过度增殖,而产短链脂肪酸的有益菌(如FaecalibacteriumRoseburia)减少。脑卒中患者肠道菌群多样性也大幅降低,特定菌群(如链球菌、乳酸菌)增多,而有益菌(如罗斯氏菌、真杆菌)减少。其他脑血管疾病患者中的肠道菌群也存在着异常的改变,如肠道菌群代谢通路中,GBPA-吡哆醛5磷酸生物合成I途径(OR = 1.48)显著增加SAH发病风险。肠道微生物通过合成生物活性代谢物影响宿主的生理功能,进而导致脑血管疾病发生,主要涉及的有三甲胺N-氧化物、脂多糖、色氨酸、短链脂肪酸等代谢物。越来越多的证据支持肠道菌群失调与脑血管疾病之间的因果关系,明确肠道菌群的异常改变可能为寻找治疗靶点提供线索。
Abstract: The pathogenesis of cerebrovascular diseases remains incompletely understood, and gut microbiota dysbiosis may play a role in its development. This review summarizes relevant studies indicating that patients with hypertension exhibit a significant reduction in gut microbiota diversity, and transplantation of gut microbiota from hypertensive patients into germ-free mice can elevate blood pressure in these animals. Pro-inflammatory bacteria such as Prevotella and Klebsiella are overrepresented, while beneficial short-chain fatty acid-producing bacteria like Faecalibacterium and Roseburia are reduced. Similarly, stroke patients show a marked decrease in gut microbiota diversity, with an increase in specific bacteria such as Streptococcus and Lactobacillus, and a decrease in beneficial bacteria like Roseburia and Eubacterium. Abnormal alterations in gut microbiota are also observed in patients with other cerebrovascular diseases. For instance, within gut microbial metabolic pathways, the GBPA-pyridoxal 5’-phosphate biosynthesis I pathway (OR = 1.48) is significantly associated with an increased risk of subarachnoid hemorrhage (SAH). Gut microbes influence host physiological functions by producing bioactive metabolites—such as trimethylamine N-oxide, lipopolysaccharide, tryptophan, and short-chain fatty acids—thereby contributing to the development of cerebrovascular diseases. Growing evidence supports a causal relationship between gut microbiota dysbiosis and cerebrovascular diseases, and elucidating these microbial alterations may provide clues for identifying therapeutic targets.
文章引用:叶铖龙, 王建莉. 肠道微生物及其代谢物与脑血管疾病关系的研究进展[J]. 临床医学进展, 2025, 15(12): 2127-2135. https://doi.org/10.12677/acm.2025.15123635

参考文献

[1] Magid-Bernstein, J., Girard, R., Polster, S., Srinath, A., Romanos, S., Awad, I.A., et al. (2022) Cerebral Hemorrhage: Pathophysiology, Treatment, and Future Directions. Circulation Research, 130, 1204-1229. [Google Scholar] [CrossRef] [PubMed]
[2] Zhang, Y., Wang, H., Sang, Y., Liu, M., Wang, Q., Yang, H., et al. (2024) Gut Microbiota in Health and Disease: Advances and Future Prospects. MedComm, 5, e70012. [Google Scholar] [CrossRef] [PubMed]
[3] Kunath, B.J., De Rudder, C., Laczny, C.C., Letellier, E. and Wilmes, P. (2024) The Oral-Gut Microbiome Axis in Health and Disease. Nature Reviews Microbiology, 22, 791-805. [Google Scholar] [CrossRef] [PubMed]
[4] Yu, X., Zhou, G., Shao, B., Zhou, H., Xu, C., Yan, F., et al. (2021) Gut Microbiota Dysbiosis Induced by Intracerebral Hemorrhage Aggravates Neuroinflammation in Mice. Frontiers in Microbiology, 12, Article ID: 647304. [Google Scholar] [CrossRef] [PubMed]
[5] Wang, Q., Dai, H., Hou, T., Hou, Y., Wang, T., Lin, H., et al. (2023) Dissecting Causal Relationships between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study. Journal of Stroke, 25, 350-360. [Google Scholar] [CrossRef] [PubMed]
[6] Li, J., Zhao, F., Wang, Y., et al. (2017) Gut Microbiota Dysbiosis Contributes to the Development of Hypertension. Microbiome, 5, Article No. 14.
[7] Luo, J., Chen, Y., Tang, G., Li, Z., Yang, X., Shang, X., et al. (2022) Gut Microbiota Composition Reflects Disease Progression, Severity and Outcome, and Dysfunctional Immune Responses in Patients with Hypertensive Intracerebral Hemorrhage. Frontiers in Immunology, 13, Article ID: 869846. [Google Scholar] [CrossRef] [PubMed]
[8] Wang, Y., Bing, H., Jiang, C., Wang, J., Wang, X., Xia, Z., et al. (2024) Gut Microbiota Dysbiosis and Neurological Function Recovery after Intracerebral Hemorrhage: An Analysis of Clinical Samples. Microbiology Spectrum, 12, e01178-24. [Google Scholar] [CrossRef] [PubMed]
[9] Sun, Y., Zhou, D., Liu, A., Zhou, Y., Zhao, Y., Yuan, Y., et al. (2025) Liangxue Tongyu Prescription Exerts Neuroprotection by Regulating the Microbiota-Gut-Brain Axis of Rats with Acute Intracerebral Hemorrhage. Brain Research Bulletin, 220, Article 111186. [Google Scholar] [CrossRef] [PubMed]
[10] Krautkramer, K.A., Kreznar, J.H., Romano, K.A., Vivas, E.I., Barrett-Wilt, G.A., Rabaglia, M.E., et al. (2016) Diet-microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues. Molecular Cell, 64, 982-992. [Google Scholar] [CrossRef] [PubMed]
[11] Singh, V., Roth, S., Llovera, G., Sadler, R., Garzetti, D., Stecher, B., et al. (2016) Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke. Journal of Neuroscience, 36, 7428-7440. [Google Scholar] [CrossRef] [PubMed]
[12] Xu, K., Gao, X., Xia, G., Chen, M., Zeng, N., Wang, S., et al. (2021) Rapid Gut Dysbiosis Induced by Stroke Exacerbates Brain Infarction in Turn. Gut, 70, 1486-1494. [Google Scholar] [CrossRef] [PubMed]
[13] Peh, A., O’Donnell, J.A., Broughton, B.R.S. and Marques, F.Z. (2022) Gut Microbiota and Their Metabolites in Stroke: A Double-Edged Sword. Stroke, 53, 1788-1801. [Google Scholar] [CrossRef] [PubMed]
[14] Sharma, V., Tan, B.Q. and Paliwal, P. (2020) Gut Microbiota and Stroke. Annals of Indian Academy of Neurology, 23, Article 155. [Google Scholar] [CrossRef] [PubMed]
[15] Pluta, R., Januszewski, S. and Czuczwar, S.J. (2021) The Role of Gut Microbiota in an Ischemic Stroke. International Journal of Molecular Sciences, 22, Article 915. [Google Scholar] [CrossRef] [PubMed]
[16] Hu, W., Kong, X., Wang, H., Li, Y. and Luo, Y. (2022) Ischemic Stroke and Intestinal Flora: An Insight into Brain-Gut Axis. European Journal of Medical Research, 27, Article No. 73. [Google Scholar] [CrossRef] [PubMed]
[17] Jeon, J., Lourenco, J., Kaiser, E.E., Waters, E.S., Scheulin, K.M., Fang, X., et al. (2020) Dynamic Changes in the Gut Microbiome at the Acute Stage of Ischemic Stroke in a Pig Model. Frontiers in Neuroscience, 14, Article ID: 587986. [Google Scholar] [CrossRef] [PubMed]
[18] Blasco, M.P., Chauhan, A., Honarpisheh, P., Ahnstedt, H., d’Aigle, J., Ganesan, A., et al. (2020) Age-Dependent Involvement of Gut Mast Cells and Histamine in Post-Stroke Inflammation. Journal of Neuroinflammation, 17, Article No. 160. [Google Scholar] [CrossRef] [PubMed]
[19] Chen, R., Wu, P., Cai, Z., Fang, Y., Zhou, H., Lasanajak, Y., et al. (2019) Puerariae Lobatae Radix with Chuanxiong Rhizoma for Treatment of Cerebral Ischemic Stroke by Remodeling Gut Microbiota to Regulate the Brain-Gut Barriers. The Journal of Nutritional Biochemistry, 65, 101-114. [Google Scholar] [CrossRef] [PubMed]
[20] Wang, H., Song, W., Wu, Q., Gao, X., Li, J., Tan, C., et al. (2021) Fecal Transplantation from db/db Mice Treated with Sodium Butyrate Attenuates Ischemic Stroke Injury. Microbiology Spectrum, 9, e0004221. [Google Scholar] [CrossRef] [PubMed]
[21] Yan, C. and Li, Y. (2024) Causal Relationships between Gut Microbiota, Inflammatory Cells/Proteins, and Subarachnoid Hemorrhage: A Multi-Omics Bidirectional Mendelian Randomization Study and Meta-Analysis. Molecular Neurobiology, 61, 8590-8599. [Google Scholar] [CrossRef] [PubMed]
[22] Fan, L., Chen, J., Pan, L., Xin, X., Geng, B., Yang, L., et al. (2022) Alterations of Gut Microbiome, Metabolome, and Lipidome in Takayasu Arteritis. Arthritis & Rheumatology, 75, 266-278. [Google Scholar] [CrossRef] [PubMed]
[23] Manabe, Y., Ishibashi, T., Asano, R., Tonomura, S., Maeda, Y., Motooka, D., et al. (2023) Gut Dysbiosis Is Associated with Aortic Aneurysm Formation and Progression in Takayasu Arteritis. Arthritis Research & Therapy, 25, Article No. 46. [Google Scholar] [CrossRef] [PubMed]
[24] Wu, M., Liao, Z., Zeng, K. and Jiang, Q. (2024) Exploring the Causal Role of Gut Microbiota in Giant Cell Arteritis: A Mendelian Randomization Analysis with Mediator Insights. Frontiers in Immunology, 14, Article ID: 1280249. [Google Scholar] [CrossRef] [PubMed]
[25] Tang, A.T., Sullivan, K.R., Hong, C.C., Goddard, L.M., Mahadevan, A. and Ren, A. (2019) Distinct Cellular Roles for PDCD10 Define a Gut-Brain Axis in Cerebral Cavernous Malformation. Science Translational Medicine, 11, eaaw3521.
[26] Ling, X., Jie, W., Qin, X., Zhang, S., Shi, K., Li, T., et al. (2022) Gut Microbiome Sheds Light on the Development and Treatment of Abdominal Aortic Aneurysm. Frontiers in Cardiovascular Medicine, 9, Article ID: 1063683. [Google Scholar] [CrossRef] [PubMed]
[27] Spence, J.D. (2022) Cardiovascular Effects of TMAO and Other Toxic Metabolites of the Intestinal Microbiome. Journal of Internal Medicine, 293, 2-3. [Google Scholar] [CrossRef] [PubMed]
[28] Zhu, W., Gregory, J.C., Org, E., Buffa, J.A., Gupta, N., Wang, Z., et al. (2016) Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Cell, 165, 111-124. [Google Scholar] [CrossRef] [PubMed]
[29] Zmora, N., Suez, J. and Elinav, E. (2018) You Are What You Eat: Diet, Health and the Gut Microbiota. Nature Reviews Gastroenterology & Hepatology, 16, 35-56. [Google Scholar] [CrossRef] [PubMed]
[30] Witkowski, M., Weeks, T.L. and Hazen, S.L. (2020) Gut Microbiota and Cardiovascular Disease. Circulation Research, 127, 553-570. [Google Scholar] [CrossRef] [PubMed]
[31] Zhu, Y., Dwidar, M., Nemet, I., Buffa, J.A., Sangwan, N., Li, X.S., et al. (2023) Two Distinct Gut Microbial Pathways Contribute to Meta-Organismal Production of Phenylacetylglutamine with Links to Cardiovascular Disease. Cell Host & Microbe, 31, 18-32.e9. [Google Scholar] [CrossRef] [PubMed]
[32] Tian, Z., Zhang, Y., Zheng, Z., Zhang, M., Zhang, T., Jin, J., et al. (2022) Gut Microbiome Dysbiosis Contributes to Abdominal Aortic Aneurysm by Promoting Neutrophil Extracellular Trap Formation. Cell Host & Microbe, 30, 1450-1463.e8. [Google Scholar] [CrossRef] [PubMed]
[33] Liao, S., Wu, J., Liu, R., Wang, S., Luo, J., Yang, Y., et al. (2020) A Novel Compound DBZ Ameliorates Neuroinflammation in LPS-Stimulated Microglia and Ischemic Stroke Rats: Role of Akt(Ser473)/GSK3β(Ser9)-Mediated Nrf2 Activation. Redox Biology, 36, Article 101644. [Google Scholar] [CrossRef] [PubMed]
[34] Ramprasath, T., Han, Y., Zhang, D., Yu, C. and Zou, M. (2021) Tryptophan Catabolism and Inflammation: A Novel Therapeutic Target for Aortic Diseases. Frontiers in Immunology, 12, Article ID: 731701. [Google Scholar] [CrossRef] [PubMed]
[35] Wang, L., Qin, N., Shi, L., Liu, R. and Zhu, T. (2024) Gut Microbiota and Tryptophan Metabolism in Pathogenesis of Ischemic Stroke: A Potential Role for Food Homologous Plants. Molecular Nutrition & Food Research, 68, Article 2400639. [Google Scholar] [CrossRef] [PubMed]
[36] Wang, J., Fan, X., Wang, J., et al. (2023) Tryptophan Metabolism in Central Nervous System Diseases: Pathophysiology and Potential Therapeutic Strategies. Aging and disease, 14, Article 858. [Google Scholar] [CrossRef] [PubMed]
[37] Qin, N., Xie, X., Deng, R., Gao, S. and Zhu, T. (2025) The Role of the Tryptophan Metabolites in Gut Microbiota-Brain Axis and Potential Treatments: A Focus on Ischemic Stroke. Frontiers in Pharmacology, 16, Article ID: 1578018. [Google Scholar] [CrossRef] [PubMed]
[38] Fang, Z., Chen, M., Qian, J., Wang, C. and Zhang, J. (2022) The Bridge between Ischemic Stroke and Gut Microbes: Short-Chain Fatty Acids. Cellular and Molecular Neurobiology, 43, 543-559. [Google Scholar] [CrossRef] [PubMed]
[39] Lee, J., d’Aigle, J., Atadja, L., Quaicoe, V., Honarpisheh, P., Ganesh, B.P., et al. (2020) Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice. Circulation Research, 127, 453-465. [Google Scholar] [CrossRef] [PubMed]
[40] Chen, R., Xu, Y., Wu, P., Zhou, H., Lasanajak, Y., Fang, Y., et al. (2019) Transplantation of Fecal Microbiota Rich in Short Chain Fatty Acids and Butyric Acid Treat Cerebral Ischemic Stroke by Regulating Gut Microbiota. Pharmacological Research, 148, Article 104403. [Google Scholar] [CrossRef] [PubMed]
[41] Liu, S., Liu, Y., Zhao, J., Yang, P., Wang, W. and Liao, M. (2022) Effects of Spermidine on Gut Microbiota Modulation in Experimental Abdominal Aortic Aneurysm Mice. Nutrients, 14, Article 3349. [Google Scholar] [CrossRef] [PubMed]