Causal relationship between gut microbiota and rheumatoid arthritis: A bidirectional 2-sample Mendelian randomization...

Area of Science:

• Microbiome research
• Immunology
• Genetics

Background:

• Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex etiology.
• The gut microbiota's role in RA pathogenesis is increasingly recognized but not fully understood.
• Bidirectional causal relationships between gut microbiota and RA require robust investigation.

Purpose of the Study:

• To evaluate the bidirectional causal relationship between gut microbiota and rheumatoid arthritis (RA) using Mendelian randomization (MR).
• To identify specific gut microbial taxa associated with increased or decreased risk of RA.
• To explore the potential of gut microbiota as therapeutic targets for RA.

Main Methods:

• Utilized large-scale genetic data for gut microbiota (n=5959) and RA (6236 cases, 147,221 controls) from Finnish cohorts.
• Performed forward and reverse Mendelian randomization analyses with stringent significance thresholds.
• Employed inverse-variance-weighted (IVW) methods, supplemented by MR-Egger, weighted median, and mode methods for robustness.
• Conducted sensitivity analyses to ensure the reliability of findings.

Main Results:

• Forward MR indicated that increased abundances of specific bacteria (e.g., Bacilli, Eubacterium_F, Christensenellales) elevate RA risk.
• Conversely, higher abundances of other bacteria (e.g., Actinobacteriota, Bifidobacterium breve) showed a protective effect against RA.
• Reverse MR revealed associations between RA and altered abundances of numerous gut microbial taxa, with no significant overlap in cross-analysis.

Conclusions:

• Specific gut microbiota compositions are causally linked to rheumatoid arthritis risk.
• Findings suggest a significant role for gut microbiota in RA pathogenesis.
• Identified microbial targets may inform novel prevention, diagnostic, and therapeutic strategies for RA.