University of Leeds-led research has identified specific changes in the gut microbiome of individuals at risk of rheumatoid arthritis, potentially discovering disease onset mechanisms.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder in which the immune system attacks the cells that line joints, making them swollen, stiff and painful. It affects over half a million people in the UK, and the World Health Organization estimates 18 million are affected worldwide. Understanding the early stages of RA has been a focus of recent research, particularly the role of the gut microbiome in disease development.
In a study, "Dynamics of the gut microbiome in individuals at risk of rheumatoid arthritis: a cross-sectional and longitudinal observational study," published in the Annals of the Rheumatic Diseases, the researchers set out to resolve the conflicting reports on Prevotellaceae abundance in the development of RA and observe the structural, functional changes in the gut microbiome in RA progressors versus non-progressors over time.
Baseline sampling included 124 individuals who tested positive for specific antibodies associated with RA (anti-CCP antibodies) and were experiencing new musculoskeletal symptoms without joint swelling. 30 of these participants progressed to RA. Longitudinal sampling over 15 months at five time points included 19 participants, with five advancing to RA.
Significant differences in Prevotellaceae abundance were observed at baseline in individuals who progressed to RA compared to non-progressors, influenced by individual RA risk factors and time to progression. Longitudinal analysis revealed gut microbiome instability in progressors starting around ten months before RA onset, a phenomenon not seen in non-progressors.
This instability may indicate a late microbial shift before the onset of clinical arthritis, with Prevotellaceae contributing but not dominating these changes.
Structural changes in the gut microbiome during RA development were associated with increased amino acid metabolism. Specific strains of Prevotellaceae were found to be enriched, while others were depleted, depending on an individual's risk profile and proximity to RA progression.
Findings suggest that past conflicting reports on Prevotellaceae overabundance are likely due to sampling within a diverse population along a dynamic disease spectrum. The current observations indicate that the gut microbiome's dynamic nature matches an individual's risk profile and transition from being at risk to developing clinical arthritis.
Understanding microbiome dynamics could significantly impact RA prediction, prevention, and personalized treatment strategies. Further research into microbiome-based diagnostics and therapeutics may explore the potential of targeting the gut microbiome in high-risk individuals for RA prevention.
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