Weizmannia coagulans NCU-33 improves rheumatoid arthritis through anti-inflammatory and immunomodulatory effects

The limitations of current rheumatoid arthritis (RA) therapies, including substantial adverse effects and economic burden, necessitate the development of safer, cost-effective adjunct treatments. Probiotic-based interventions targeting the gut-joint axis hold therapeutic promise, yet their precise mechanisms of action remain incompletely understood. This study investigated the therapeutic efficacy and underlying mechanisms of W. coagulans NCU-33 in a collagen-induced arthritis (CIA) mouse model. Intervention with NCU-33 significantly attenuated clinical arthritic scores, joint swelling, and histopathological damage. Mechanistically, NCU-33 exerted a coordinated, multi-pronged effect: in joint tissue, it suppressed TLR2/MyD88/NF-κB signaling, reducing pro-inflammatory cytokines TNF-α and IL-6; systemically, it modulated Notch signaling in splenic lymphocytes, thereby rectifying the pathogenic Th17/Treg imbalance; and in the gut, it restructured the microbiota by enriching beneficial Lactobacillus spp., which enhanced intestinal barrier integrity and elevated short-chain fatty acid levels. In summary, W. coagulans NCU-33 ameliorates experimental arthritis through an integrated, multi-target mechanism that concurrently regulates local inflammation, systemic immune homeostasis, and gut ecosystem equilibrium. These findings provide robust preclinical evidence supporting the clinical development of W. coagulans NCU-33 as a novel, mechanism-driven probiotic therapy for RA via modulation of the gut-joint axis.