Abstract
Kawasaki disease (KD) is a multi-systemic vasculitis of unknown etiology that occurs mainly in children, and the disturbance of gut microbiota is generally believed to cause a hyperimmune reaction triggering KD. The aim of the study was to investigate the alterations in the fecal microbiota and assess its relationship with systemic inflammation. Totally 30 KD children were enrolled and followed up for 6 months, with another group of 30 age- and sex-matched healthy children as controls. Phylotype profiles of fecal microbial communities were analyzed using 16S rRNA gene sequencing. Serum inflammatory markers were detected by flow cytometer. We showed that KD children exhibited a significant reduction in fecal microbial diversity in the acute phase compared with the healthy controls. Enterococcus, Acinetobacter, Helicobacter, Lactococcus, Staphylococcus and Butyricimonas in acute KD children were significantly higher than the healthy children. Levels of systemic inflammation biomarkers, including IL-2, IL-4, IL-6, IL-10, TNF-α, and INF-γ, were significantly elevated in the acute KD children. Altered microbiota genera Enterococcus and Helicobacter abundances were shown to be correlated positively with IL-6, which were never previously reported in KD. This study suggested that gut microbiota alteration is closely associated with systemic inflammation, which provides a new perspective on the etiology and pathogenesis of KD.
Highlights
Kawasaki disease (KD) is a multi-systemic vasculitis of unknown etiology that occurs mainly in children, and the disturbance of gut microbiota is generally believed to cause a hyperimmune reaction triggering KD
The levels of IL-2, IL-4, IL-6, IL-10, TNF-α and INF-γ in KD children were significantly elevated in the acute phase compared with healthy controls
We investigated the alteration in the gut microbiota composition between the acute and non-acute phases of KD using linear discriminant analysis effect size (LEfSe), and observed that Enterococcus, Leuconostoc, Megamonas, Helicobacter, Morganella and Lactococcus were significantly increased in acute KD children, whereas the short chain fatty acids (SCFA) producing microbiota including Blautia, Prevotella, Dialister, Clostridium, Roseburia, Anaerostipes, Ruminococcus, and Dorea were significantly enriched in non-acute KD children (Fig. 6)
Summary
Kawasaki disease (KD) is a multi-systemic vasculitis of unknown etiology that occurs mainly in children, and the disturbance of gut microbiota is generally believed to cause a hyperimmune reaction triggering KD. The aim of the study was to investigate the alterations in the fecal microbiota and assess its relationship with systemic inflammation. We showed that KD children exhibited a significant reduction in fecal microbial diversity in the acute phase compared with the healthy controls. This study suggested that gut microbiota alteration is closely associated with systemic inflammation, which provides a new perspective on the etiology and pathogenesis of KD. We sequenced the V3–V4 hypervariable regions of the 16S rRNA gene to gain a comprehensive profile of gut microbiota composition and to investigate its relationship with systemic inflammation in KD children
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