Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, Sichuan, China.
Front Immunol. 2024 Jul 22;15:1416185. doi: 10.3389/fimmu.2024.1416185. eCollection 2024.
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.
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.
First, significant changes had been observed between KD and their controls. We found that the decrease of , , , and and the increase of pathogenic bacteria , , and 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 , the enrichment of 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.
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.
川崎病（KD）已被认为是世界上最常见的儿科心血管疾病之一。然而，KD 的分子机制尚未完全阐明，导致疾病管理混乱，并为预后预测提供了宝贵的线索。肠道微生物组的紊乱已在几种心血管疾病和炎症情况下被识别。因此，阐明 KD 中肠道微生物组的特征，并证明其在调节静脉注射免疫球蛋白（IVIG）耐药和冠状动脉损伤中的潜在作用迫在眉睫。
本研究共纳入 96 例 KD 患儿和 62 例对照。从 KD 患者中采集了 140 份粪便样本，包括接受 IVIG 治疗前后、有无早期冠状动脉损伤和 IVIG 耐药的患者。在 IVIG 给药前后采集粪便样本并储存在-80°C。然后，使用 Illumina NovaSeq 6000 平台进行宏基因组分析。之后，鉴定了比较之间的不同菌株和功能差异。
首先，在 KD 患者和对照组之间观察到显著变化。我们发现， 、 、 、 和致病性细菌 、 、 的减少，可能与 KD 的发病密切相关。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治疗效果的结果相关。其中，KD 患者 IVIG 耐药与 、 、 减少和抗生素耐药基因的富集有关。此外，我们的数据还揭示了一些潜在的与 KD 患者冠状动脉损伤相关的病原微生物组。
这些结果有力地证明了 KD 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 发病机制的原因，并对 KD 的预后产生重大影响。
