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.

The authors have declared no competing interest.

This study was funded by NIH T32 GM136554 and F31 AI167538 awards to M.E.M. Studies were supported by a Burroughs Wellcome Fund Next Gen Pregnancy Initiative (NGP10103), NIH R01 (DK128053), and NIH U19 (AI157981) awards to K.A.P. This work was supported in part by NCI Cancer Center Support Grant (P30CA125123) to the Antibody-based Proteomics Core.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Board for Baylor College of Medicine (H-47537) and Harris Health System (23-05-3085) gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.