Abstract
The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from the fecal samples of 93 RA patients and 16 healthy subjects. Microbiota profiling was conducted through 16S rRNA sequencing and bioinformatics analyses. The effects of Bifidobacterium strains on human peripheral blood mononuclear cells and collagen-induced arthritis (CIA) mice were assessed. Significant differences in gut microbiota composition were observed in patients with different RF levels. The relative abundance of Bifidobacterium and Collinsella was lower in RF-high than in RF-low and RF-negative RA patients, while the relative abundance of Clostridium of Ruminococcaceae family was higher in RF-high than in RF-low and RF-negative patients. Among 10 differentially abundant Bifidobacterium, B. longum RAPO exhibited the strongest ability to inhibit IL-17 secretion. Oral administration of B. longum RAPO in CIA mice, obese CIA, and humanized avatar model significantly reduced RA incidence, arthritis score, inflammation, bone damage, cartilage damage, Th17 cells, and inflammatory cytokine secretion. Additionally, B. longum RAPO significantly inhibited Th17 cells and Th17-related genes—IL-17A, IRF4, RORC, IL-21, and IL-23R—in the PBMCs of rheumatoid arthritis patients. Our findings suggest that B. longum RAPO may alleviate RA by inhibiting the production of IL-17 and other proinflammatory mediators. The safety and efficacy of B. longum RAPO in patients with RA and other autoimmune disorders merit further investigation.
Highlights
Rheumatoid factor (RF) is an autoantibody detected in approximately 80% of patients with the autoimmune disease rheumatoid arthritis (RA) [1, 2]
We investigated the gut microbiota composition in RA patients with varying RF levels and the effects of B. longum RAPO on RA
Previous studies have shown that targeted therapies can modulate the gut microbiota composition and increase the abundance of beneficial microorganisms [30]
Summary
Rheumatoid factor (RF) is an autoantibody detected in approximately 80% of patients with the autoimmune disease rheumatoid arthritis (RA) [1, 2]. Mounting evidence suggests the critical role of human RF as an IgG antigen in RA development and pathogenesis [9]. The deposition of immune complexes containing RF in the joints activates the complement, resulting in type III hypersensitivity reactions and causing joint inflammation [15]. During this inflammatory reaction, the membrane attack complex consisting of C5a and C5b-C9 is formed due to complement activation [15]. RF has been identified as a predictor of drug response in patients with RA treated with anti-TNFa drugs [7]
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