Effects of Qingluo Tongbi Decoction on Gut Flora of Rats with Adjuvant-Induced Arthritis and the Underlying Mechanism

Abstract

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. Recent studies show that gut flora plays an important role in regulating the systemic immune response, and gut dysbacteria are linked with systemic chronic inflammation in the development of RA. Our previous results found that Qingluo Tongbi decoction (QLT) can treat RA effectively. The present study explored the effect of QLT on gut flora in an adjuvant-induced arthritis (AA) rat model. Thirty rats were divided randomly into three groups: A control group, a model group, and a treatment group (n = 10 per group). The rats in the model group were injected with complete Freund's adjuvant (FCA), while the treatment group received FCA combined with QLT treatment. After 27 days, the gut flora was profiled by 16S rRNA gene sequencing. The levels of cadherin-11, IL-17α, TLR2, and TLR4 proteins in the synovial tissues were detected by western blotting (WB). The results showed that QLT treatment significantly inhibited raw swelling during the 15-27 d period compared with the model group. QLT treatment reversed the ten altered bacterial genera in the model group, and three families (Lachnospiraceae, Eubacteriaceae, and Leuconostocaceae) were closely related to QLT treatment based on linear discriminant analysis (LDA). Functional prediction showed seven types of predicted functions were related to the QLT treatment, and WB results showed that QLT treatment reversed the increased expression levels of cadherin-11, IL-17α, TLR2, and TLR4 in synovial tissues significantly. The expression levels of cadherin-11, IL-17α, and TLR2 correlated negatively with the abundance of Staphylococcus and Candidatus-Saccharimonas. Therefore, RA development was related to gut dysbiosis, and QLT effectively ameliorated RA with decreased inflammatory responses regulated by the gut flora.