Dynamics of the gut microbiome in individuals at risk of rheumatoid arthritis: a cross-sectional and longitudinal observational study 2024

Abstract
Objectives This work aimed to resolve the conflicting reports on Prevotellaceae abundance in the development of rheumatoid arthritis (RA) and to observe structural, functional and temporal changes in the gut microbiome in RA progressors versus non-progressors.

Methods Individuals at risk of RA were defined by the presence of anticyclic citrullinated protein (anti-CCP) antibodies and new musculoskeletal symptoms without clinical synovitis. Baseline sampling included 124 participants (30 progressed to RA), with longitudinal sampling of 19 participants (5 progressed to RA) over 15 months at five timepoints. Gut microbiome taxonomic alterations were investigated using 16S rRNA amplicon sequencing and confirmed with shotgun metagenomic DNA sequencing on 49 samples.

Results At baseline, CCP+ at risk progressors showed significant differences in Prevotellaceae abundance compared with non-progressors, contingent on intrinsic RA risk factors and time to progression. Longitudinal sampling revealed gut microbiome instability in progressors 10 months before RA onset, a phenomenon absent in non-progressors. This may indicate a late microbial shift before RA onset, with Prevotellaceae contributing but not dominating these changes. Structural changes in the gut microbiome during arthritis development were associated with increased amino acid metabolism.

Conclusion These data suggest conflicting reports on Prevotellaceae overabundance are likely due to sampling within a heterogeneous population along a dynamic disease spectrum, with certain Prevotellaceae strains/clades possibly contributing to the establishment and/or progression of RA. Gut microbiome changes in RA may appear at the transition to clinical arthritis as a late manifestation, and it remains unclear whether they represent a primary or secondary phenomenon.

Dynamics of the gut microbiome in individuals at risk of rheumatoid arthritis: a cross-sectional and longitudinal observational study | Annals of the Rheumatic Diseases

article about the research:
Gut microbiome changes linked to onset of rheumatoid arthritis among at-risk individuals