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

Ectopic colonization by oral bacteria as an emerging theme in health and disease

“…A few recent studies have pointed towards an association between autoimmune diseases and ectopic colonization by oral bacteria and started to shed light on the underlying molecular mechanisms: A first study in a Chinese cohort of 49 patients with RA and 25 healthy patients observed that absolute abundance of F. nucleatum in the feces correlated with RA severity. This association was especially strong for known biomarkers as RA such as serum levels of the proinflammatory cytokines IL-6 and TNFα, C-reactive protein as well as changes to the erythrocytes sedimentation state (a blood test to indirectly assess for systemic inflammation) (Hong et al 2023 ). On an experimental level, oral administration of F. nucleatum to a mouse model of collagen-induced arthritis resulted in increased arthritis severity, characterized by higher levels of proinflammatory cytokines in the serum, higher bone erosion and infiltration of macrophages and neutrophils in the joints.…”

“…On an experimental level, oral administration of F. nucleatum to a mouse model of collagen-induced arthritis resulted in increased arthritis severity, characterized by higher levels of proinflammatory cytokines in the serum, higher bone erosion and infiltration of macrophages and neutrophils in the joints. Moreover, this phenotype was reversible upon antibiotic depletion of F. nucleatum from the intestinal tract of these mice (Hong et al 2023 ). At molecular level, the induction in inflammation seems to be due to F. nucleatum -secreted outer membrane vesicles containing the adhesin protein FadA, an essential factor for F. nucleatum dissemination to distant sites.…”

Bacterial extracellular vesicles: A position paper by the microbial vesicles task force of the Chinese society for extracellular vesicles

“…Fusobacterium nucleatum OMVs contain the virulence determinant FadA that translocates into the joints, triggering local inflammatory responses. The results indicate that Fusobacterium nucleatum OMVs play a causal role in exacerbating rheumatoid arthritis (RA) and offer potential therapeutic targets for improving the clinical outcomes of RA 10 . Another study found that Akkermansia muciniphila ‐derived extracellular vesicles (AmEVs) were transported from the gastrointestinal (GI) tract to the placenta and alleviated pre‐eclamptic symptoms in mice with Preeclampsia (PE).…”

“…BEVs are considered as bioactive cargo delivery modes, demonstrating great potential in biomedical applications. First, since specific components such as nucleic acids, proteins, virulence factors and LPS are closely related to their pathogenicity, changes in their quality or quantity help to clarify the pathogenesis of their parent bacteria, which suggest that BEVs may be used in disease diagnosis 10 . Second, BEVs are promising tools in the field of drug delivery systems and vaccines.…”

Outer membrane vesicles from Fusobacterium nucleatum aggravate rheumatoid arthritis

“…Researchers have identified a new interaction mode between gut microbiota and immune homeostasis of the synovium in modulating autoimmune responses in rheumatoid arthritis (RA), according to a new study published in Cell Host & Microbe 1 . The study findings provide valuable information and insights into the causes of inflammation of RA and suggest Fusobacterium nucleatum ( F. nucleatum ) and its outer membrane vesicles (OMVs) as promising therapeutic targets for clinically ameliorating RA.…”