Lactobacillus helveticus Alleviates Collagen-Induced Arthritis in Rats Through Inflammation Modulation and Gut Microbiota Regulation

<b>Background</b>: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis, with growing evidence underscoring the role of gut microbiota dysbiosis and impaired intestinal barrier function in driving inflammation and immune dysregulation. <b>Methods</b>: Four strains of <i>Lactobacillus helveticus</i> (CCFM1501, DSCAB9M6, CCFM1263, DYNDL451) were evaluated in a collagen-induced arthritis (CIA) rat model. <b>Results</b>: <i>L. helveticus</i> CCFM1501 exhibited the most pronounced therapeutic benefits. It significantly attenuated paw swelling and synovial hyperplasia and reduced serum levels of total collagen-II-specific IgG and its subclasses (IgG1, IgG2a, IgG2b), pro-inflammatory cytokines (IL-1β, IL-6, IL-17A, TNF-α), and matrix metalloproteinases (MMP-2, MMP-3, MMP-9) while elevating anti-inflammatory IL-10. Moreover, CCFM1501 enhanced intestinal barrier integrity by upregulating tight junction proteins (ZO-1, Occludin, Claudin-1), increased concentrations of short-chain fatty acids (acetic, propionic and butyric acids), and positively restructured gut microbiota composition. <b>Conclusions</b>: These findings demonstrate that <i>L. helveticus</i> CCFM1501 is associated with the alleviation of CIA, which may be linked to multi-faceted mechanisms including immunomodulation, intestinal barrier repair, SCFA promotion, and microbial homeostasis restoration. These results suggest its potential as a targeted probiotic strategy for RA management and justify further clinical translation.