A cross-sectional analysis of the vaginal microenvironment in rheumatoid arthritis

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. Self-collected vaginal swabs and questionnaires on dietary, menstrual, and health information were obtained from 36 RA and 50 demographically-matched control women, 18-63 years of age. Medication regimen, along with disease activity and severity, was captured for the RA cohort. Vaginal swabs were subjected to long-read 16S rRNA gene sequencing, multiplex cytokine analyses, and quantification of rheumatoid factor, C-reactive protein, and anti-citrullinated protein antibodies (ACPAs). Vaginal microbial richness and Peptoniphilus and Prevotella, among other rare taxa, were elevated in RA versus control samples. Vaginal interleukin (IL)-18 and epidermeal growth factor (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. When faceted by diet and menopausal status, several immune markers were increased in the RA vaginal environment. Vaginal ACPAs were higher in the RA group and positively correlated with Streptococcus and multiple vaginal inflammatory cytokines. We describe vaginal microbial and immunological differences in women with RA, particularly when accounting for diet and menopausal status, and disease activity and severity. This work opens a new avenue in the multidisciplinary approach to RA patient care.IMPORTANCERheumatoid arthritis (RA) is a debilitating autoimmune disease that disproportionately impacts women. Although it is widely recognized that microbial factors can trigger or aggravate RA symptoms and alter disease progression, it is unknown whether RA impacts the microbiota and immune responses within the vaginal tract. In this study, we compare the vaginal microbial communities and immune (cytokine) profiles in women with RA and healthy controls. Within RA patients, we also evaluate how these factors relate to clinical RA symptoms, RA biomarkers, and RA-related medications. Overall, we found that RA was associated with increased microbial diversity and multiple inflammatory markers, some of which were also associated with RA biomarkers and disease activity. These findings suggest that the vaginal tract may be an additional tissue impacted by RA disease, and further research is needed to understand mechanisms and potential for therapeutic intervention.