Abstract
BACKGROUND: We aimed to investigate the gut microbiota of patients with established rheumatoid arthritis (RA) who have been managed with disease-modifying anti-rheumatic drugs (DMARDs) for a long time. We focused on factors that might affect composition of the gut microbiota. Furthermore, we investigated whether gut microbiota composition predicts future clinical responses to conventional synthetic DMARDs (csDMARDs) in patients with an insufficient response to initial therapy. METHODS: We recruited 94 patients with RA and 30 healthy participants. Fecal gut microbiome was analyzed by 16S rRNA amplificon sequencing; the resulting raw reads were processed based on QIIME2. Calypso online software was used for data visualization and to compare microbial composition between groups. For RA patients with moderate-to-high disease activity, treatment was changed after stool collection, and responses were observed 6 months later. RESULTS: The composition of the gut microbiota in patients with established RA was different from that of healthy participants. Young RA patients (< 45 years) had reduced richness, evenness, and distinct gut microbial compositions when compared with older RA patients and healthy individuals. Disease activity and rheumatoid factor levels were not associated with microbiome composition. Overall, biological DMARDs and csDMARDs, except sulfasalazine and TNF inhibitors, respectively, were not associated with the gut microbial composition in patients with established RA. However, the combination of Subdoligranulum and Fusicatenibacter genera was associated with a future good response to second-line csDMARDs in patients who showed an insufficient response to first-line csDMARDs. CONCLUSION: Gut microbial composition in patients with established RA is different from that in healthy individuals. Thus, the gut microbiome has the potential to predict responses of some RA patients to csDMARDs.