Full-length 16S sequences of self-collected vaginal swabs of women with and without rheumatoid arthritis
Objective: The human microbiota is implicated in the development and progression of rheumatoid arthritis (RA). Given the increased RA burden in women, and well-known correlations between the vaginal microbiota and local inflammation, we seek to understand the vaginal microenvironment in the context of RA pathology.  Methods: Self-collected vaginal swabs and questionnaires on dietary and health practices were obtained from 36 RA and 50 demographically-matched control women, 18-63 years of age. Additionally, medication regimen and disease activity and severity were captured for the RA cohort. Vaginal swabs were subjected to full-length 16S rRNA gene sequencing, multiplex cytokine analyses, and quantification of rheumatoid factor, c-reactive protein, and anti-citrullinated protein antibodies (ACPAs).   Results: Vaginal microbial richness and genera Peptoniphilus and Prevotella, among other rare taxa, were elevated in RA versus control samples. Vaginal IL-18 and EGF levels were increased in the RA group; IL-18 correlated with multiple microbial features whereas EGF levels were not associated with bacterial composition or other host factors. Within the RA cohort, decreased relative abundance of Streptococcus was associated with joint pathologies, and Lactobacillus gasseri was lower in individuals with serum detection of ACPAs and rheumatoid factor. Vaginal ACPAs were higher in the RA group and positively correlated with Streptococcus and multiple vaginal inflammatory cytokines.   Conclusions: We describe vaginal microbial and immunological differences in women with RA, particularly when accounting for diet and menopausal status, disease activity and severity, and medication use. This work opens a new avenue in the multidisciplinary approach to RA patient care.