Fusobacterium nucleatum aggravates rheumatoid arthritis through FadA-containing outer membrane vesicles

Rheumatoid arthritis (RA) is an autoimmune disorder that has been associated with the gut microbiota. However, whether and how the gut microbiota plays a pathogenic role in RA remains unexplored. Here, we observed that Fusobacterium nucleatum is enriched in RA patients and positively associated with RA severity. F. nucleatum similarly aggravates arthritis in a mouse model of collagen-induced arthritis (CIA). F. nucleatum outer membrane vesicles (OMVs) containing the virulence determinant FadA translo-cate into the joints, triggering local inflammatory responses. Specifically, FadA acts on synovial macro-phages, resulting in the activation of the Rab5a GTPase involved in vesicle trafficking and inflammatory pathways and YB-1, a key regulator of inflammatory mediators. OMVs containing FadA and heightened Rab5a-YB-1 expression were observed in RA patients compared with controls. These findings suggest a causal role of F. nucleatum in aggravating RA and provide promising therapeutic targets for clinically ameliorating RA.

Automated summary

The gut microbiota of RA patients is enriched with Fusobacterium nucleatum, which is positively associated with the severity of RA. F. nucleatum aggravates arthritis and triggers local inflammatory responses by translocating into the joints through outer membrane vesicles containing the virulence determinant FadA. This study reveals the causal role of F. nucleatum in aggravating RA and identifies potential therapeutic targets for RA treatment.