Fecal microbiota in children with juvenile idiopathic arthritis treated with methotrexate or etanercept

BACKGROUND: Alterations in the composition of the fecal microbiota in children with juvenile idiopathic arthritis (JIA) have been observed in several studies, but it has not been determined whether the standard treatment for JIA changes the composition or function of the microbiota. The first-line disease-modifying anti-rheumatic drug for treatment of JIA is usually methotrexate, followed or supplemented by anti-tumor necrosis factor alpha drugs, such as etanercept. The aim of this study was to investigate the effects of methotrexate and etanercept treatments on the fecal microbiota and the fecal short-chain fatty acids (SCFAs) in children with JIA. METHODS: In this multicenter study, the composition of fecal microbiota from 45 treatment-naïve children with JIA was compared with that from 29 children treated with methotrexate and 12 children treated with etanercept. We also made pairwise comparisons of 15 children sampled before and during methotrexate treatment and 7 children sampled before and during etanercept treatment. The microbiota was determined using sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene. Alpha-diversity, community composition, and relative abundances of bacterial taxa were analyzed in all comparisons. Analyses of fecal SCFAs, using a high-performance liquid chromatograph, were performed for the pairwise comparisons. RESULTS: We did not find any significant differences in α-diversity or community composition of microbiota. However, principal coordinate analysis indicated a change in community composition in 7 of the 15 paired samples before and during methotrexate and 2 of the 7 paired samples before and during etanercept. Comparisons of the relative abundance of taxa revealed minor differences before and during treatment with methotrexate or etanercept, but they were not significant after correction for multiple analyses, and the unpaired and paired analyses did not show similar changes. There were no significant differences in levels of fecal SCFAs before and during treatment with methotrexate or etanercept. CONCLUSIONS: Treatment with methotrexate or etanercept had minor, but no significant or consistent changes either on composition of microbiota or on levels of SCFAs, suggesting that these changes are not related to the therapeutic effects of methotrexate or etanercept.