A Shifted Composition and Dysbiosis of Urinary Microbiota in Rheumatoid Arthritis: A Case-Control Study

Background: Emerging evidence has emphasized the functional of microbiota in the etiopathogenesis of rheumatoid arthritis (RA). Previously we and other groups have demonstrated that the urinary infection was implicated in the pathogenesis of RA. However, the profile of urinary microbiota and its association with RA remains to be investigated.Methods: The study cohort consisted of 39 patients with RA, including 8 treatment-naïve patients, and 37 age- and sex-matched healthy controls. The clean midstreams of urine samples were collected from both groups. The microbial profiles and bacterial loads of urinary microbiota were identified and quantified by 16S ribosomal RNA (16S rRNA) gene sequencing and quantitative PCR, respectively. The compositions of urinary microbiota and its associations with clinical and molecular characteristics were analyzed. The urinary metabolites were detected by gas chromatography.Findings: Compared to healthy controls, the urinary microbiota from RA patients displayed an increase in microbial richness with a decrease in microbial dissimilarity. There were 40 altered genera with absolute quantities in patients with RA, including 31 enriched (Proteus, Faecalibacterium, Bacteroides, etc.) and 9 deficient genera (Arcanobacterium, Rothia, Megasphaera, Ureaplasma, etc.). These RA-associated urinary taxa achieved a performance power of 84.6% for discriminating RA patients from healthy controls. Notably, the RA-enriched, but not deficient genera, were correlated with elevated disease duration, anti-CCP antibodies, joint damages, and increase of circulating LPS binding protein (LBP) and soluble CD14. Furthermore, the compositions of the urinary metabolites, including proline, citric acid and oxalic acid, were significantly different in RA patients from healthy controls. These RA-associated urinary metabolites showed close correlations with urinary microbiota.Interpretation: An increased microbial richness and shifted compositional profiles are found in the urinary microbiota of RA patients, which is strongly associated with immunological and metabolic changes in RA.Funding: National Natural Science Foundation of China and Beijing Municipal Science & Technology Commission.Declaration of Interest: None to declare. Ethical Approval: Approval for the study was obtained from the Medical Ethics Committee of Peking University People’s Hospital.