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Bifidobacterium pseudocatenulatum-Mediated Bile Acid Metabolism to Prevent Rheumatoid Arthritis via the Gut-Joint Axis

Early intervention in rheumatoid arthritis (RA) is critical for optimal treatment, but initiation of pharmacotherapy to prevent damage remains unsatisfactory currently. Manipulation of the gut microbiome and microbial metabolites can be effective in protecting against RA. Thus, probiotics can be utilized to explore new strategies for preventing joint damage. The aim of this study was to explore the metabolites and mechanisms by which Bifidobacterium pseudocatenulatum affects RA. Based on 16S rRNA sequencing and UPLC-MS/MS assays, we focused on bile acid (BA) metabolism. In a collagen-induced arthritis (CIA) mouse model, B. pseudocatenulatum prevented joint damage by protecting the intestinal barrier and reshaped gut microbial composition, thereby elevating bile salt hydrolase (BSH) enzyme activity and increasing the levels of unconjugated secondary BAs to suppress aberrant T-helper 1/17-type immune responses; however, these benefits were eliminated by the Takeda G protein-coupled receptor 5 (TGR5) antagonist SBI-115. The results suggested that a single bacterium, B. pseudocatenulatum, can prevent RA, indicating that prophylactic administration of probiotics may be an effective therapy.

 

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The study aims to explore the mechanisms by which Bifidobacterium pseudocatenulatum affects rheumatoid arthritis (RA) by focusing on bile acid metabolism. The researchers used a collagen-induced arthritis (CIA) mouse model to evaluate the effects of B. pseudocatenulatum on joint damage prevention and gut microbial composition. The study found that B. pseudocatenulatum protected the intestinal barrier and elevated bile salt hydrolase (BSH) enzyme activity, which increased the levels of unconjugated secondary bile acids to suppress aberrant T-helper 1/17-type immune responses. These effects were eliminated by the Takeda G protein-coupled receptor 5 (TGR5) antagonist SBI-115. The results suggest that B. pseudocatenulatum can prevent RA and that probiotics may be an effective therapy for RA.

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