The antioxidant strain Lactiplantibacillus plantarum BX62 alleviates rheumatoid arthritis via balancing immune homeostasis and modulating NLRP3/Caspase-1/IL-1β and AKT/mTOR pathways

This study explored the effect of antioxidant Lactiplantibacillus plantarum BX62 (2×10 9 CFU/ml) on RA and elucidated its underlying mechanisms using a collagen induced arthritis rat model. Results showed L. plantarum BX62 reduced oxidative stress, decreased the levels of inflammatory cytokines in the serum, and increased anti-inflammatory interleukin-10 levels. Bone damage mitigation was confirmed via histology and micro-computed tomography analyses. Furthermore, L. plantarum BX62 restored immune balance and CD4+/CD8+ T cell ratio in the spleen. Downregulations of NLRP3, Cleaved Caspased-1, Cleaved IL-1β, RANKL, p-AKT, p-mTOR, and p62, and upregulations of OPG and Beclin-1 proteins were also observed in L . plantarum BX62 group. Meanwhile, The stable organ coefficients of L. plantarum BX62 demonstrated its safety for oral administration. Overall, L. plantarum BX62 demonstrated preventive effects against RA progression by reducing oxidative stress, modulating NLRP3/Caspase-1/IL-1β, AKT/mTOR pathways, balancing autophagy, and enhancing bone protection; thus, making it a formidable probiotic strain for curing RA. • L. plantarum BX62 as an antioxidant can effectively inhibit the development of rheumatoid arthritis in rats. • L. plantarum BX62 can alleviate the characteristics of rheumatoid arthritis by balancing the immune homeostasis in rats. • L. plantarum BX62 can regulate NLRP3/Caspase-1/IL-1β and AKT/mTOR signaling pathways to exert anti-arthritic function. • L. plantarum BX62 is expected to replace methotrexate at a dose of 7.6 mg/kg/week for the prevention and treatment of RA.