Therapeutic efficacy of Bacillus clausii via NFκB/Nrf-2/HO-1 pathway modulation in a CFA-induced arthritis model

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by dysregulated cytokine signalling, oxidative stress, and persistent synovial inflammation. Nearly 0.24–1 % of people worldwide suffer from RA, caused by complex genetic and environmental factors leading to joint destruction and inflammation cascades. Methods: Using a complete Freund's adjuvant (CFA)-induced murine model of arthritis, this study investigated the immunomodulatory and antioxidant properties of Bacillus clausii (1 × 10⁸ CFU/animal/day, orally) administered as a pre-treatment, concurrent, and adjunct intervention over 28 days. Results: It was evident from histological and radiological investigations that B. clausii considerably reduced joint damage, arthritic index scores, and paw swelling. Better nociceptive and affective results from behavioural tests suggested anti-nociceptive and anti-depressive effects. Furthermore, B. clausii altered critical inflammatory pathways and considerably decreased oxidative stress by upregulating HO-1 and Nrf-2; these effects were confirmed by downregulating IFN-γ, IL-17, IL-6, and phosphorylated NF-κB. Conclusions: These findings suggest that B. clausii has a variety of therapeutic effects in RA by targeting oxidative and inflammatory mediators without producing long-term toxicity. Due to its favourable safety and efficacy profile, it may be a valuable adjunct to conventional anti-arthritic treatments.