Characterization Of Gut Microbiota In Systemic-onset Juvenile Idiopathic Arthritis

BACKGROUND:Juvenile idiopathic arthritis(JIA)is the most common chronic rheumatic disease of childhood.Systemic-onset JIA(SoJIA)is one of most serious subtypes.Although the pathogenesis of SoJIA remains unclear,several studies have suggested a correlation between gut dysbiosis and JIA.Further understanding of the intestinal microbiome may help to establish alternative ways in which to treat,or even prevent,the disease.AIM:To explore alterations in fecal microbiota profiles in SoJIA patients and to evaluate the correlations between gut microbiota composition and clinical parameters of disease activity,METHODS:We conducted an observational single-center study at the Pediatric Department of Peking Union Medical College Hospital between June 2017 and December 2018.Children diagnosed with SoJIA at our institution,and who were followed up for a minimum period of ten months,were recruited for the study.Healthy children was recruited as control group during the same period Clinical data and stool samples were collected from SoJIA patients when they visited the hospital.Patients were divided into active group or inactive groups according to Wallace criteria at the time of sample collection.RESULTS:The total cohort comprised 64 children.The SoJIA group included 17 active(9 males)and 15 inactive(7 males)consecutively recruited children aged from 6 to 16 years;the control group consisted of 32 children(18 males)aged from 5 to 16 years.No significant differences in age and gender were observed among the three groups.A total of 5,270,328 effective tags were obtained by high-throughput sequencing from 64 specimens obtained from SoJIA patients and control subjects.The average number of effective tags per sample was 82,349.Among all samples,tags with a similarly level of 97%were clustered into 2,216 OTUs.The results showed that there was significant difference among the three groups in observed species and Chao 1,which were highest in Active-SoJIA,followed by Inactive-SoJIA and then the healthy subjects(HS)group.Assessment of the Shannon and Simpson indices showed no remarkable differences among the three groups.PCoA on unweighted UniFrac showed that both SoJIA samples(active and inactive)were more similar to each other than to the HS sample.PERMANOVA confirmed the differences among samples:Active-SoJIA vs.HS(P=0.001)and Inactive-SoJIA vs.HS(P=0.001);there was no significant difference between Active-SoJIA and Inactive-SoJIA.We observed a lower Firmicutes/Bacteroidetes ratio in SoJIA patients(3.28±4.47 in Active-SoJIA,5.36±8.39 in Inactive-SoJIA,and 5.67±3.92 in HS,Active-SoJIA vs.HS,P=0.048).We also observed decreased abundances of Riiminococcaceae(14.9%in Active-SoJIA,17.3%in Inactive-SoJIA,and 22.8%in HS;Active-SoJIA vs.HS P=0.005)and Faecalibacterium(5.1%in Active-SoJIA,9.9%in Inactive-SoJIA,and 13.0%in HS;Active-SoJIA vs.HS P=0.000)in SoJIA compared with healthy subjects.By contrast,the abundance of Bacteroidaceae was Active-SoJIA>Inactive-SoJIA>HS(16.5%in Active-SoJIA,12.8%in Inactive-SoJIA,and 9.7%in HS;Active-SoJIA vs.HS P=0.03).The Spearman correlation analysis revealed a negative correlation between Proteobacteria,Enterobacteriaceae and juvenile arthritis disease activity score on 27 joints(JADAS-27).CONCLUSION:The composition of the intestinal microbiota is different in SoJIA patients compared with healthy children.The dysbiosis presents partial restoration in inactive status patients.