肠道微生物与川崎病冠状动脉损伤关系研究进展
Research Progress on the Relationship between Gut Microbiota and Coronary Artery Injury in Kawasaki Disease
DOI: 10.12677/bp.2024.144026, PDF,   
作者: 程榆林：重庆医科大学公共卫生学院，重庆
关键词: 肠道微生物；川崎病；冠状动脉；Gut Microbiota； Kawasaki Disease； Coronary Artery
摘要: 川崎病是一种急性炎症性疾病，主要发生在5岁以下的婴幼儿中，其最严重的并发症是冠状动脉损伤。川崎病的发病机制尚未完全明确，但越来越多的证据表明肠道微生物在川崎病发生发展中发挥着重要作用。例如，肠道微生物群的失衡可能通过干扰免疫系统来促进川崎病的发展，而补充某些可以产生短链脂肪酸的肠道微生物能缓解川崎病引起的损伤，尤其是冠状动脉损伤。本研究通过查阅国内外文献，综述了肠道微生物在川崎病发生发展中的作用，为今后探索川崎病的新的防治方案提供依据。
Abstract: Kawasaki disease is an acute inflammatory disease that mainly occurs in infants and young children under the age of 5, and its most serious complication is coronary artery injury. The pathogenesis of Kawasaki disease is not fully understood, but increasing evidence suggests that gut microbiota plays an important role in the occurrence and development of Kawasaki disease. For example, the imbalance of gut microbiota may promote the development of Kawasaki disease by interfering with the immune system, while supplementing certain gut microbiota that can produce short chain fatty acids can alleviate the damage caused by Kawasaki disease, especially coronary artery injury. This study reviewed the role of gut microbiota in the occurrence and development of Kawasaki disease by reviewing domestic and foreign literature, providing a basis for exploring new prevention and treatment strategies for Kawasaki disease in the future.
文章引用：程榆林. 肠道微生物与川崎病冠状动脉损伤关系研究进展[J]. 生物过程, 2024, 14(4): 210-217. https://doi.org/10.12677/bp.2024.144026

参考文献

[1] Kuo, H., Yu, H., Juo, S.H., Yang, K.D., Wang, Y., Liang, C., et al. (2010) Journal of Human Genetics, 56, 161-165. [Google Scholar] [CrossRef] [PubMed]
[2] Noval Rivas, M. and Arditi, M. (2020) Kawasaki Disease: Pathophysiology and Insights from Mouse Models. Nature Reviews Rheumatology, 16, 391-405. [Google Scholar] [CrossRef] [PubMed]
[3] Valtuille, Z., Lefevre-Utile, A., Ouldali, N., Beyler, C., Boizeau, P., Dumaine, C., et al. (2023) Calculating the Fraction of Kawasaki Disease Potentially Attributable to Seasonal Pathogens: A Time Series Analysis. E Clinical Medicine, 61, Article 102078. [Google Scholar] [CrossRef] [PubMed]
[4] McCrindle, B.W., Rowley, A.H., Newburger, J.W., Burns, J.C., Bolger, A.F., Gewitz, M., et al. (2017) Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals from the American Heart Association. Circulation, 135, e927-e999. [Google Scholar] [CrossRef] [PubMed]
[5] Sabharwal, T., Manlhiot, C., Benseler, S.M., Tyrrell, P.N., Chahal, N., Yeung, R.S.M., et al. (2009) Comparison of Factors Associated with Coronary Artery Dilation Only versus Coronary Artery Aneurysms in Patients with Kawasaki Disease. The American Journal of Cardiology, 104, 1743-1747. [Google Scholar] [CrossRef] [PubMed]
[6] McCrindle, B.W., Li, J.S., Minich, L.L., Colan, S.D., Atz, A.M., Takahashi, M., et al. (2007) Coronary Artery Involvement in Children with Kawasaki Disease. Circulation, 116, 174-179. [Google Scholar] [CrossRef] [PubMed]
[7] Suzuki, A., Kamiya, T., Yasuo, O. and Kuroe, K. (1991) Extended Long Term Follow-Up Study of Coronary Arterial Lesions in Kawasaki Disease. Journal of the American College of Cardiology, 17, A33. [Google Scholar] [CrossRef] 
[8] Gerber, M.A., Baltimore, R.S., Eaton, C.B., Gewitz, M., Rowley, A.H., Shulman, S.T., et al. (2009) Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal Pharyngitis. Circulation, 119, 1541-1551. [Google Scholar] [CrossRef] [PubMed]
[9] Orenstein, J.M., Shulman, S.T., Fox, L.M., Baker, S.C., Takahashi, M., Bhatti, T.R., et al. (2012) Three Linked Vasculopathic Processes Characterize Kawasaki Disease: A Light and Transmission Electron Microscopic Study. PLOS ONE, 7, e38998. [Google Scholar] [CrossRef] [PubMed]
[10] Wang, H., Tang, Y., Yan, W., Xu, Q., Li, X. and Qian, W. (2022) Breastfeeding Has No Protective Effects on the Development of Coronary Artery Lesions in Kawasaki Disease: A Retrospective Cohort Study. BMC Pediatrics, 22, Article No. 353. [Google Scholar] [CrossRef] [PubMed]
[11] Bäckhed, F., Roswall, J., Peng, Y., Feng, Q., Jia, H., Kovatcheva-Datchary, P., et al. (2015) Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host & Microbe, 17, 690-703. [Google Scholar] [CrossRef] [PubMed]
[12] Koenig, J.E., Spor, A., Scalfone, N., Fricker, A.D., Stombaugh, J., Knight, R., et al. (2010) Succession of Microbial Consortia in the Developing Infant Gut Microbiome. Proceedings of the National Academy of Sciences, 108, 4578-4585. [Google Scholar] [CrossRef] [PubMed]
[13] Chen, S., Tsai, C., Lee, Y., Lin, C., Huang, K., Chao, H., et al. (2017) Intestinal Microbiome in Children with Severe and Complicated Acute Viral Gastroenteritis. Scientific Reports, 7, Article No. 46130. [Google Scholar] [CrossRef] [PubMed]
[14] Minot, S.S., Mayer-Blackwell, K., Fiore-Gartland, A., Johnson, A., Self, S., Bhatti, P., et al. (2024) Species-and Subspecies-Level Characterization of Health-Associated Bacterial Consortia That Colonize the Human Gut during Infancy. Gut Microbes, 16, Article 2414975. [Google Scholar] [CrossRef] [PubMed]
[15] 刘进娜, 张婵娟, 李娜. 补中益气汤调控JAK2/STAT3信号通路对气虚发热证大鼠肠道菌群、免疫功能及神经功能的影响[J]. 陕西中医, 2023, 44(5): 571-574.
[16] 周倩沁, 吴军华, 邱海燕. 川崎病病因及发病机制的研究进展[J]. 浙江医学, 2019, 41(13): 1443-1446.
[17] Huang, S., Huang, S., Weng, K., Chien, K., Lin, C. and Huang, Y. (2019) Update on Association between Kawasaki Disease and Infection. Journal of the Chinese Medical Association, 82, 172-174. [Google Scholar] [CrossRef] [PubMed]
[18] 李瑞燕, 李晓辉. 川崎病病因学研究进展[J]. 心血管病学进展, 2010, 31(4): 616-620.
[19] Yamashiro, Y., Nagata, S., Ohtsuka, Y., Oguchi, S. and Shimizu, T. (1996) Microbiologic Studies on the Small Intestine in Kawasaki Disease. Pediatric Research, 39, 622-624. [Google Scholar] [CrossRef] [PubMed]
[20] Eladawy, M., Dominguez, S.R., Anderson, M.S. and Glodé, M.P. (2013) Kawasaki Disease and the Pediatric Gastroenterologist. Journal of Pediatric Gastroenterology and Nutrition, 56, 297-299. [Google Scholar] [CrossRef] [PubMed]
[21] Esposito, S., Polinori, I. and Rigante, D. (2019) The Gut Microbiota-Host Partnership as a Potential Driver of Kawasaki Syndrome. Frontiers in Pediatrics, 7, Article 124. [Google Scholar] [CrossRef] [PubMed]
[22] Fukazawa, M., Fukazawa, M., Nanishi, E., Nishio, H., Ichihara, K. and Ohga, S. (2020) Previous Antibiotic Use and the Development of Kawasaki Disease: A Matched Pair Case-Control Study. Pediatrics International, 62, 1044-1048. [Google Scholar] [CrossRef] [PubMed]
[23] 沈男, 王莹, 王兴翠, 等. 川崎病对儿童肠道菌群的影响[J]. 基础医学与临床, 2019, 39(5): 636-640.
[24] Teramoto, Y., Akagawa, S., Hori, S., Tsuji, S., Higasa, K. and Kaneko, K. (2023) Dysbiosis of the Gut Microbiota as a Susceptibility Factor for Kawasaki Disease. Frontiers in Immunology, 14, Article 1268453. [Google Scholar] [CrossRef] [PubMed]
[25] 钱范宇, 章启豪, 岑建柯, 等. 低聚果糖通过调整肠道菌群改善川崎病小鼠冠状动脉损伤的机制[J]. 温州医科大学学报, 2021, 51(6): 431-436.
[26] 高娜, 贺改涛, 穆志龙, 等. 川崎病患儿肠道菌群构成及分布与其冠状动脉病变的相关性分析[J]. 现代生物医学进展, 2023, 23(20): 3969-3973.
[27] Zhou, C., Li, L., Li, T., Sun, L., Yin, J., Guan, H., et al. (2020) SCFAS Induce Autophagy in Intestinal Epithelial Cells and Relieve Colitis by Stabilizing Hif-1α. Journal of Molecular Medicine, 98, 1189-1202. [Google Scholar] [CrossRef] [PubMed]
[28] 吕露露, 张雪静. 耳塞和眼罩对重症监护室患者谵妄和睡眠质量影响的Meta分析[J]. 中国全科医学, 2019, 22(32): 3956-3961+3968.
[29] Bartolomaeus, H., Balogh, A., Yakoub, M., Homann, S., Markó, L., Höges, S., et al. (2019) Short-Chain Fatty Acid Propionate Protects from Hypertensive Cardiovascular Damage. Circulation, 139, 1407-1421. [Google Scholar] [CrossRef] [PubMed]
[30] Chen, Y., Xu, C., Huang, R., Song, J., Li, D. and Xia, M. (2018) Butyrate from Pectin Fermentation Inhibits Intestinal Cholesterol Absorption and Attenuates Atherosclerosis in Apolipoprotein E-Deficient Mice. The Journal of Nutritional Biochemistry, 56, 175-182. [Google Scholar] [CrossRef] [PubMed]
[31] Wang, Y., Xu, Y., Yang, M., Zhang, M., Xiao, M. and Li, X. (2020) Butyrate Mitigates TNF-Α-Induced Attachment of Monocytes to Endothelial Cells. Journal of Bioenergetics and Biomembranes, 52, 247-256. [Google Scholar] [CrossRef] [PubMed]
[32] Kasahara, K., Krautkramer, K.A., Org, E., Romano, K.A., Kerby, R.L., Vivas, E.I., et al. (2018) Interactions between Roseburia Intestinalis and Diet Modulate Atherogenesis in a Murine Model. Nature Microbiology, 3, 1461-1471. [Google Scholar] [CrossRef] [PubMed]
[33] Kaneko, K., Akagawa, S., Akagawa, Y., Kimata, T. and Tsuji, S. (2020) Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota. Frontiers in Immunology, 11, Article 1616. [Google Scholar] [CrossRef] [PubMed]
[34] Wang, N., Chen, Z., Zhang, F., Zhang, Q., Sun, L., Lv, H., et al. (2022) Intravenous Immunoglobulin Therapy Restores the Quantity and Phenotype of Circulating Dendritic Cells and CD4+ T Cells in Children with Acute Kawasaki Disease. Frontiers in Immunology, 13, Article 802690. [Google Scholar] [CrossRef] [PubMed]
[35] Wang, F., Qian, F., Zhang, Q., Zhao, J., Cen, J., Zhang, J., et al. (2023) The Reduced SCFA-Producing Gut Microbes Are Involved in the Inflammatory Activation in Kawasaki Disease. Frontiers in Immunology, 14, Article 1124118. [Google Scholar] [CrossRef] [PubMed]
[36] 石树文, 田雯. 肠道微生物群与儿童川崎病[J]. 心血管病学进展, 2020, 41(6): 608-610+621.
[37] Porritt, R.A., Markman, J.L., Maruyama, D., Kocaturk, B., Chen, S., Lehman, T.J.A., et al. (2020) Interleukin-1 Beta-Mediated Sex Differences in Kawasaki Disease Vasculitis Development and Response to Treatment. Arteriosclerosis, Thrombosis, and Vascular Biology, 40, 802-818. [Google Scholar] [CrossRef] [PubMed]
[38] McCrindle, B.W. and Manlhiot, C. (2020) Sars-Cov-2-Related Inflammatory Multisystem Syndrome in Children. Journal of the American Medical Association, 324, 246-248. [Google Scholar] [CrossRef] [PubMed]
[39] Chen, J., Yue, Y., Wang, L., Deng, Z., Yuan, Y., Zhao, M., et al. (2020) Altered Gut Microbiota Correlated with Systemic Inflammation in Children with Kawasaki Disease. Scientific Reports, 10, Article No. 14525. [Google Scholar] [CrossRef] [PubMed]
[40] Bonten, M.J. and Willems, R.J. (2012) Vancomycin-Resistant Enterococcus—Chronicle of a Foretold Problem. Nederlands Tijdschrift voor Geneeskunde, 156, A5233.
[41] Treitman, A.N., Yarnold, P.R., Warren, J. and Noskin, G.A. (2005) Emerging Incidence of Enterococcus Faecium among Hospital Isolates (1993 to 2002). Journal of Clinical Microbiology, 43, 462-463. [Google Scholar] [CrossRef] [PubMed]
[42] Guiton, P.S., Hung, C.S., Hancock, L.E., Caparon, M.G. and Hultgren, S.J. (2010) Enterococcal Biofilm Formation and Virulence in an Optimized Murine Model of Foreign Body-Associated Urinary Tract Infections. Infection and Immunity, 78, 4166-4175. [Google Scholar] [CrossRef] [PubMed]
[43] Kusuda, T., Nakashima, Y., Murata, K., Kanno, S., Nishio, H., Saito, M., et al. (2014) Kawasaki Disease-Specific Molecules in the Sera Are Linked to Microbe-Associated Molecular Patterns in the Biofilms. PLOS ONE, 9, e113054. [Google Scholar] [CrossRef] [PubMed]
[44] Bazemore, T.C., Maskarinec, S.A., Zietlow, K., Hendershot, E.F. and Perfect, J.R. (2016) Familial Adenomatous Polyposis Manifesting as Lactococcus Endocarditis: A Case Report and Review of the Association of Lactococcus with Underlying Gastrointestinal Disease. Case Reports in Infectious Diseases, 2016, 1-5. [Google Scholar] [CrossRef] [PubMed]
[45] Nagata, S. (2019) Causes of Kawasaki Disease—From Past to Present. Frontiers in Pediatrics, 7, Article 18. [Google Scholar] [CrossRef] [PubMed]
[46] Papathanasopoulos, A. and Camilleri, M. (2010) Dietary Fiber Supplements: Effects in Obesity and Metabolic Syndrome and Relationship to Gastrointestinal Functions. Gastroenterology, 138, 65-72. [Google Scholar] [CrossRef] [PubMed]
[47] Nagata, S., Yamashiro, Y., Ohtsuka, Y., Shimizu, T., Sakurai, Y., Misawa, S., et al. (2009) Heat Shock Proteins and Super-Antigenic Properties of Bacteria from the Gastrointestinal Tract of Patients with Kawasaki Disease. Immunology, 128, 511-520. [Google Scholar] [CrossRef] [PubMed]
[48] Flem, E., Mouawad, C., Palmu, A.A., Platt, H., Johnson, K.D., McIntosh, E.D., et al. (2024) Indirect Protection in Adults ≥18 Years of Age from Pediatric Pneumococcal Vaccination: A Review. Expert Review of Vaccines, 23, 997-1010. [Google Scholar] [CrossRef] [PubMed]
[49] Rello, J., Ricart, M., Mirelis, B., Quintana, E., Gurgui, M., Net, A. and Prats, G. (1994) Nosocomial Bacteremia in a Medical-surgical Intensive Care Unit: Epidemiologic Characteristics and Factors Influencing Mortality in 111 Episodes. Intensive Care Medicine, 20, 94-98. [Google Scholar] [CrossRef]