The Role Of Gut Microbiota In The Inflammatory Response To Kawasaki Disease

Objective: The aim of the study was to investigate the alterations in the fecal microbiota and assess its relationship with systemic inflammation in children Kawasaki disease（KD）.Methods: We enrolled 30 KD children from April 2017 to January 2019 and followed up for 6 months,fecal samples and serum samples were collected during acute phase,a second fecal samples was also collected from KD children at 6 months after disease onset（within 15 days beforehand or afterwards）.30 age-and sex-matched healthy children were selected as healthy controls.Fecal samples were collected.Phylotype profiles of fecal microbial communities were analyzed by using bacterial 16 S rRNA sequencing.Serum inflammatory cytokines were detected by flow cytometer.Results:1.Our results showed that compared to the healthy controls,KD children exhibited a significant reduction in fecal microbial diversity（P<0.05）,but there were no significant differences in microbial richness between acute KD children and healthy controls（P>0.05）.2.Enterococcus,Acinetobacter,Helicobacter,Lactococcus,Staphylococcus and Butyricimonas were significantly more abundant in acute KD children than in healthy children（LDA>2.0,P<0.05）.3.Short-chain fatty acid（SCFA）producing microbiota such as Prevotella,Dialister,Clostridium,Eubacterium,Roseburia and Megasphaerawere significantly reduced in acute KD children as compared with those of healthy controls（LDA>2.0,P<0.05）.Compared with healthy controls,the SCFA producing microbiota which included Blautia,Prevotella,Dialister,Clostridium,Roseburia,Anaerostipes,Ruminococcus,and Dorea were significantly enriched in non-acute KD children（LDA>2.0,P<0.05）.4.Compared with healthy controls,levels of biomarkers of systemic inflammation,including IL-2,IL-4,IL-6,IL-10,TNF-α,and IFN-γ,were significantly elevated in the acute KD children（P<0.05）.5.Altered abundance of the microbiota genera Enterococcus was shown to be correlated positively with IL-2 and IL-6（r=0.39,P=0.01;r=0.39,P=0.02）and Helicobacter was correlated positively with IL-6（r=0.37,P=0.00）,while Clostridium_sensu_stricto₁ was correlated negatively with TNF-α（r=-0.38,P=0.02）.Conclusion: 1.The gut microbial diversity was significantly decreased in the acute phase of KD,indicated that the gut microbiota of children with Kawasaki disease was disordered.2.The relative abundance of Enterococcus,Acinetobacter,Helicobacter,Lactococcus,Staphylococcus and Butyricimonas were significantly enriched in acute KD children,with a reduction in short chain fatty acids producing microbiota,which promoted the gut microbiota dysbiosisassociated with KD.3.The disturbance in the composition of gut microbiota was associated with systemic inflammation in KD children,which provide new insight into the etiology of KD and will help us to understand its pathogenesis better.