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剖析肠道:肠道机制在川崎病发病机制中的关键作用。

Unraveling the gut: the pivotal role of intestinal mechanisms in Kawasaki disease pathogenesis.

作者信息

Tao Enfu, Lang Dandan

机构信息

Department of Neonatology and Neonatal Intensive Care Unit (NICU), Wenling Maternal and Child Health Care Hospital, Wenling, Zhejiang, China.

Department of Pediatrics, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, Guangdong, China.

出版信息

Front Immunol. 2024 Nov 26;15:1496293. doi: 10.3389/fimmu.2024.1496293. eCollection 2024.

DOI:10.3389/fimmu.2024.1496293
PMID:39664384
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11633670/
Abstract

Kawasaki disease (KD), an acute systemic vasculitis that primarily affects children under 5 years of age, is the leading cause of acquired heart disease in this age group. Recent studies propose a novel perspective on KD's etiology, emphasizing the gastrointestinal (GI) tract, particularly the role of gut permeability. This review delves into how disruptions in gut barrier function trigger systemic inflammatory responses, exacerbate vascular inflammation, and contribute to coronary artery aneurysms. Evidence suggests that children with KD often exhibit increased gut permeability, leading to an imbalance in gut immunity and subsequent gut barrier damage. These changes impact vascular endothelial cells, promoting platelet aggregation and activation, thereby advancing severe vascular complications, including aneurysms. Additionally, this review highlights the correlation between GI symptoms and increased resistance to standard treatments like intravenous immunoglobulin (IVIG), indicating that GI involvement may predict therapeutic outcomes. Advocating for a new paradigm, this review calls for integrated research across gastroenterology, immunology, and cardiology to examine KD through the lens of GI health. The goal is to develop innovative therapeutic interventions targeting the intestinal barrier, potentially revolutionizing KD management and significantly improving patient outcomes.

摘要

川崎病(KD)是一种主要影响5岁以下儿童的急性全身性血管炎,是该年龄组后天性心脏病的主要原因。最近的研究对KD的病因提出了新的观点,强调胃肠道(GI),特别是肠道通透性的作用。这篇综述深入探讨了肠道屏障功能的破坏如何引发全身炎症反应、加剧血管炎症并导致冠状动脉瘤。有证据表明,KD患儿通常表现出肠道通透性增加,导致肠道免疫失衡和随后的肠道屏障损伤。这些变化影响血管内皮细胞,促进血小板聚集和激活,从而引发包括动脉瘤在内的严重血管并发症。此外,这篇综述强调了胃肠道症状与对静脉注射免疫球蛋白(IVIG)等标准治疗的耐药性增加之间的相关性,表明胃肠道受累可能预测治疗结果。倡导一种新的范式,这篇综述呼吁胃肠病学、免疫学和心脏病学进行综合研究,以通过肠道健康的视角审视KD。目标是开发针对肠道屏障的创新治疗干预措施,可能会彻底改变KD的管理并显著改善患者预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fedc/11633670/f5c78fdf89f3/fimmu-15-1496293-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fedc/11633670/bb1b3dcf8105/fimmu-15-1496293-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fedc/11633670/4764ab2b7251/fimmu-15-1496293-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fedc/11633670/f5c78fdf89f3/fimmu-15-1496293-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fedc/11633670/bb1b3dcf8105/fimmu-15-1496293-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fedc/11633670/4764ab2b7251/fimmu-15-1496293-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fedc/11633670/f5c78fdf89f3/fimmu-15-1496293-g003.jpg

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Rab7-dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis.Rab7 依赖性调控杯状细胞蛋白 CLCA1 调节胃肠道稳态。
Elife. 2024 Apr 9;12:RP89776. doi: 10.7554/eLife.89776.
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Association of Previous Antibiotics Use and Kawasaki Disease: A Cohort Study of 106,908 Patients.先前抗生素使用与川崎病的关联:一项 106908 例患者的队列研究。
Pediatr Infect Dis J. 2024 Jul 1;43(7):643-650. doi: 10.1097/INF.0000000000004335. Epub 2024 Mar 25.
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The roles of ABCB1/P-glycoprotein drug transporters in regulating gut microbes and inflammation: insights from animal models, old and new.
ABCB1/P-糖蛋白药物转运体在调节肠道微生物和炎症中的作用:来自新旧动物模型的见解。
Philos Trans R Soc Lond B Biol Sci. 2024 May 6;379(1901):20230074. doi: 10.1098/rstb.2023.0074. Epub 2024 Mar 18.
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Intestinal mucosal barrier: a potential target for traditional Chinese medicine in the treatment of cardiovascular diseases.肠道黏膜屏障:中药治疗心血管疾病的潜在靶点。
Front Pharmacol. 2024 Feb 26;15:1372766. doi: 10.3389/fphar.2024.1372766. eCollection 2024.
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The etiologies of Kawasaki disease.川崎病的病因。
J Clin Invest. 2024 Mar 1;134(5):e176938. doi: 10.1172/JCI176938.
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Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota-gut-brain axis.胃肠道和大脑屏障:解锁微生物群-肠道-大脑轴上的沟通之门。
Nat Rev Gastroenterol Hepatol. 2024 Apr;21(4):222-247. doi: 10.1038/s41575-023-00890-0. Epub 2024 Feb 14.
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Risk factors and an early predictive model for Kawasaki disease shock syndrome in Chinese children.川崎病休克综合征中国儿童的危险因素及早期预测模型。
Ital J Pediatr. 2024 Feb 3;50(1):22. doi: 10.1186/s13052-024-01597-x.
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Jaundice-predominant manifestation of Kawasaki disease in children.黄疸是儿童川崎病的主要表现。
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