Effects of changes on gut microbiota in children with acute Kawasaki disease.
Effects of changes on gut microbiota in children with acute Kawasaki disease.
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作者：
Shen J;Ding Y;Yang Z;Zhang X;Zhao M
川崎病（Kawasaki disease， KD）是儿童早期的一种急性发热性疾病。这种疾病的确切病因尚不清楚。目前对KD的研究多局限于易感基因、感染、免疫等方面。然而，关于肠道菌群与KD之间相关性的研究很少。诊断为急性KD的儿童和同一时期接受体格检查的儿童被纳入研究对象。入院时采集受试者外周静脉血和粪便。通过高通量测序对粪便样本进行细菌分类分析。通过α多样性、β多样性、线性判别分析和LDA效应量分析，比较KD患儿和健康儿童肠道菌群的丰度、多样性、组成和特征差异。采用血常规、生化分析、免疫球蛋白定量检测。与对照组相比，KD组肠道菌群群落丰富度和结构显著降低（Chao1丰富度估计值，KD组平均215.85，对照组平均725.76,p < 0.01； Shannon多样性指数，KD组平均3.32，对照组平均5.69,p < 0.05）。LEfSe分析鉴定出两株与KD显著相关的细菌：拟杆菌门（Bacteroidetes）和Dorea。健康儿童中拟杆菌群丰富（KD组平均0.16，对照组平均0.34,p < 0.05）。Dorea在健康儿童中也很丰富，但在KD患儿中很少存在（KD患儿平均0.002，对照组平均0.016,p < 0.05）。与对照组相比，KD组IgA和IgG水平降低（KD组IgA中位数为0.68 g/L，对照组中位数为1.06 g/L, p < 0.001； KD组IgG中位数为6.67 g/L，对照组中位数为9.71 g/L, p < 0.001）， IgE和IgM水平无显著变化。急性KD患儿发生肠道菌群失调，可能与KD的病因或发病机制有关。值得注意的是，我们首次发现Dorea（一种产氢细菌）在急性KD患儿中显著减少。总之，我们的研究结果为基于肠道微生态的KD预防或诊断提供了理论依据。
Kawasaki disease (KD) is an acute febrile illness of early childhood. The exact etiology of the disease remains unknown. At present, research on KD is mostly limited to susceptibility genes, infections, and immunity. However, research on the correlation between gut microbiota and KD is rare. Children with a diagnosis of acute KD and children undergoing physical examination during the same period were included. At the time of admission, the subjects’ peripheral venous blood and feces were collected. Faecal samples were analyzed for bacterial taxonomic content via high-throughput sequencing. The abundance, diversity, composition, and characteristic differences of the gut microbiota in KD and healthy children were compared by alpha diversity, beta diversity, linear discriminant analysis and LDA effect size analysis. Blood samples were used for routine blood examination, biochemical analysis, and immunoglobulin quantitative detection. Compared with the control group, the community richness and structure of gut microbiota in the KD group was significantly reduced (Chao1 richness estimator, mean 215.85 in KD vs. mean 725.76 in control, p < 0.01; Shannon diversity index, mean 3.32 in KD vs. mean 5.69 in control, p < 0.05). LEfSe analysis identified two strains of bacteria significantly associated with KD: Bacteroidetes and Dorea. Bacteroidetes were enriched in healthy children (mean 0.16 in KD vs. mean 0.34 in control, p < 0.05). Dorea was also enriched in healthy children but rarely existed in children with KD (mean 0.002 in KD vs. mean 0.016 in control, p < 0.05). Compared with the control, IgA and IgG in the KD group decreased (IgA, median 0.68 g/L in KD vs. median 1.06 g/L in control, p < 0.001; IgG, median 6.67 g/L in KD vs. median 9.71 g/L in control, p < 0.001), and IgE and IgM levels were not significantly changed. Dysbiosis of gut microbiota occurs in children with acute KD and may be related to the etiology or pathogenesis of KD. It is worth noting that for the first time, we found that Dorea, a hydrogen-producing bacterium, was significantly reduced in children with acute KD. Overall, our results provide a theoretical basis for the prevention or diagnosis of KD based on intestinal microecology.
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