关键词: IVIG resistance Kawasaki disease coronary artery lesions diagnosis metagenomic analysis prognosis

Mesh : Humans Mucocutaneous Lymph Node Syndrome / microbiology immunology Gastrointestinal Microbiome / genetics Male Metagenomics / methods Female Child, Preschool Infant Feces / microbiology Immunoglobulins, Intravenous / therapeutic use Metagenome Child Bacteria / classification genetics isolation & purification Case-Control Studies

来  源:   DOI:10.3389/fimmu.2024.1416185   PDF(Pubmed)

Abstract:
UNASSIGNED: Kawasaki disease (KD) has been considered as the most common required pediatric cardiovascular diseases among the world. However, the molecular mechanisms of KD were not fully underlined, leading to a confused situation in disease management and providing precious prognosis prediction. The disorders of gut microbiome had been identified among several cardiovascular diseases and inflammation conditions. Therefore, it is urgent to elucidate the characteristics of gut microbiome in KD and demonstrate its potential role in regulating intravenous immunoglobulin (IVIG) resistance and coronary artery injuries.
UNASSIGNED: A total of 96 KD children and 62 controls were enrolled in the study. One hundred forty fecal samples had been harvested from KD patients, including individuals before or after IVIG treatment, with or without early coronary artery lesions and IVIG resistance. Fecal samples had been collected before and after IVIG administration and stored at -80°C. Then, metagenomic analysis had been done using Illumina NovaSeq 6000 platform. After that, the different strains and functional differences among comparisons were identified.
UNASSIGNED: First, significant changes had been observed between KD and their controls. We found that the decrease of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides uniformis, and Bacteroides ovatus and the increase of pathogenic bacteria Finegoldia magna, Abiotrophia defectiva, and Anaerococcus prevotii perhaps closely related to the incidence of KD. Then, metagenomic and responding functional analysis demonstrated that short-chain fatty acid pathways and related strains were associated with different outcomes of therapeutic efficacies. Among them, the reduction of Bacteroides thetaiotaomicron, the enrichment of Enterococcus faecalis and antibiotic resistance genes had been found to be involved in IVIG resistance of KD. Moreover, our data also revealed several potential pathogenetic microbiome of that KD patients with coronary artery lesions.
UNASSIGNED: These results strongly proved that distinct changes in the gut microbiome of KD and the dysfunction of gut microbiomes should be responsible for the pathogenesis of KD and significantly impact the prognosis of KD.
摘要:
川崎病(KD)被认为是世界上最常见的儿科心血管疾病。然而,KD的分子机制没有得到充分强调,导致疾病管理混乱,并提供宝贵的预后预测。已经在几种心血管疾病和炎症状况中确定了肠道微生物组的紊乱。因此,迫切需要阐明KD中肠道微生物组的特征,并证明其在调节静脉免疫球蛋白(IVIG)抵抗和冠状动脉损伤中的潜在作用。
共有96名KD儿童和62名对照纳入研究。从KD患者身上收集了一百四十份粪便样本,包括IVIG治疗之前或之后的个体,有或没有早期冠状动脉病变和IVIG抵抗。在IVIG给药之前和之后收集粪便样品并储存在-80°C。然后,使用IlluminaNovaSeq6000平台进行了宏基因组分析。之后,鉴定了比较中的不同菌株和功能差异。
首先,在KD和对照组之间观察到显著变化。我们发现Akkermansia粘虫的减少,普氏粪杆菌,均匀拟杆菌,卵形拟杆菌和病原菌的增加,营养不良,和缺氧球菌可能与KD的发病率密切相关。然后,宏基因组和响应功能分析表明,短链脂肪酸途径和相关菌株与不同的治疗效果相关.其中,拟杆菌的减少,已发现粪肠球菌和抗生素耐药基因的富集与KD的IVIG耐药有关。此外,我们的数据还揭示了患有冠状动脉病变的KD患者的几种潜在的致病微生物组.
这些结果有力地证明了KD的肠道微生物组的明显变化和肠道微生物组的功能障碍可能是KD的发病机理,并显着影响KD的预后。
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