Astragalus Polysaccharides Alleviate Inflammatory Damage in Murine Rheumatoid Arthritis by Modulating Th17/Treg Balance via the Gut–Joint Axis

Astragalus polysaccharides (APSs) have demonstrated protective effects in RA models; however, the underlying microbe–host crosstalk remains unclear. In this study, collagen-induced arthritis (CIA) was established in mice, followed by prophylactic and therapeutic APS administration. The following were then assessed: articular histopathology, splenic Th17/Treg frequencies via flow cytometry, serum and joint cytokine profiles via ELISA and immunohistochemistry, gut microbial metagenomes, and bone erosion via Safranin O–fast green staining. It was found that APS treatment significantly attenuated joint inflammation and bone destruction, rebalanced the Th17/Treg ratio, and reduced pro-inflammatory cytokines (TNF-α and IL-17) while elevating anti-inflammatory IL-10 both systemically and locally. Subsequently, fecal microbiota from APS-treated donor mice was transplanted via oral gavage into CIA recipient mice. APS reversed RA-associated gut dysbiosis by enriching Ligilactobacillus, Lactobacillus, Limosilactobacillus, and Bacteroides, and these microbial shifts closely paralleled diminished articular inflammation and preserved bone architecture. Collectively, these findings indicate that APS mitigates RA progression by reconfiguring the gut microbial ecosystem—favoring beneficial taxa while curbing pathobionts—thereby restoring intestinal homeostasis, normalizing the Th17/Treg axis, and suppressing systemic and articular inflammatory responses.