Associations of upper respiratory mucosa microbiota with Rheumatoid arthritis, autoantibodies, and disease activity

by Young Bin Joo, Juho Lee, Yune-Jung Park, So-Young Bang, Kwangwoo Kim, Hye-Soon Lee

The lung is recognized as a site for initiating the formation of self-antigen and autoimmune responses in rheumatoid arthritis (RA). We aimed to investigate the association of upper respiratory microbiota with RA, autoantibody production, and disease activity. Forty-six patients with RA and 17 controls were examined. Nasopharyngeal swab samples were sequenced for microbiome profiling using the V3–V4 region of the 16S rRNA gene. The microbial diversity and relative abundance were compared between RA patients and controls. Correlation analyses were conducted to evaluate the relationship between microbial abundance and clinical markers such as autoantibodies and disease activity. Microbial diversity analysis revealed no major differences between RA patients and healthy controls. However, beta diversity analysis indicated a subtle distinction in microbial composition (unweighted UniFrac distance) between the two groups (P = 0.03), hinting at a minor subset of microbiota associated with disease status. Differential abundance analysis uncovered specific taxa at various taxonomic levels, including Saccharibacteria (TM7) [O-1] (P_FDR = 2.53 × 10⁻²), TM7 [F-1] (P_FDR = 5.20 × 10⁻³), Microbacterium (P_FDR = 3.37 × 10⁻⁴), and Stenotrophomonas (P_FDR = 2.57 × 10⁻³). The relative abundance of ten genera correlated significantly with anti-cyclic citrullinated peptide (anti-CCP) antibody levels (P_FDR < 0.05) and 11 genera were significantly associated with disease activity markers, including ESR, CRP, DAS28-ESR, and DAS-CRP (P_FDR < 0.05). In particular, Saccharibacteria TM7 [G-3] and Peptostreptococcaceae [XI] [G-1] were correlated with all disease activity biomarkers. Dysbiosis in the upper respiratory mucosa is associated with RA, anti-CCP antibody levels, and disease activity.