Gut microbiota dysbiosis and metabolic alterations in rheumatoid arthritis: a barrier to periodontal repair.

OBJECTIVE

To investigate the impact of rheumatoid arthritis (RA) on periodontal healing and the underlying mechanisms.

METHODS

Mandibular periodontal bone defect (PBD) and collagen-induced arthritis (CIA) models were established in male Sprague-Dawley rats aged 6 weeks, assigned to four groups: control (CON), CIA, PBD and CIA+PBD. Periodontal repair was evaluated at 1, 3 and 6 weeks. To examine the contribution of gut microbiota, pseudo-germ-free rats with PBD received 3-week faecal microbiota transplantation (FMT) from either healthy or CIA donors. Arthritis severity was assessed by paw thickness and arthritis index, while bone microarchitecture was examined by micro-CT and histology. Gut microbiota and metabolites were analysed using 16S ribosomal RNA high-throughput sequencing and untargeted metabolomics.

RESULTS

CIA was found to significantly impair periodontal bone healing and suppress osteogenesis-related markers, including runt-related transcription factor 2 and alkaline phosphatase. Compared with CON rats, CIA and PBD, CIA+PBD groups exhibited gut microbial dysbiosis and metabolic alterations, particularly in arachidonic acid and tryptophan pathways. FMT from CIA donors further increased osteoclast numbers and delayed bone regeneration. Furthermore, gut-derived factors from CIA animals were associated with increased macrophage expression of pro-inflammatory cytokines, including tumour necrosis factor-alpha and interleukin-1 beta.

CONCLUSION

Overall, RA-related gut microbiota dysbiosis and metabolic disturbances are linked to impaired periodontal healing, potentially through enhanced inflammatory responses. This study highlights a microbiome-immune-metabolic axis that may influence periodontal regeneration in RA.