Angelica sinensis polysaccharide improves rheumatoid arthritis by modifying the expression of intestinal Cldn5, Slit3 and Rgs18 through gut microbiota

Rheumatoid arthritis (RA) is an autoimmune disease with a high incidence. Recent studies have demonstrated that diet can contribute to the development and progression of RA. Indeed, non-starch polysaccharides (NSPs) were known to be related to the improvement of RA. In this study, the collagen-induced rats were administrated with Angelica sinensis polysaccharide (ASP) at 200 mg/kg (L), 400 mg/kg (M), or 800 mg/kg (H). Results showed that ASP could reduce joint swelling and significantly inhibit anti-CII-antibodies and pro-inflammatory factors in RA, H group showed the best treatment among them. Further analysis using 16S rDNA sequencing suggested that ASP could shape the gut microbiota composition. Several key bacteria, including norank_f__norank_o__Clostridia_UCG-014, Lactobacillus, norank_f__Oscillospiraceae, and norank_f__Desulfovibrionaceae, were found to be related to the development of RA. The colonic transcriptome showed that ASP could restore RA-induced intestinal dysfunction, such as tight junction disarrangement, by upregulating Cldn5. The balance between osteoblasts and osteoclasts might be modified by regulating the expression of Slit3 and Rgs18 to alleviate RA, which may be correlated with gut microbiota. Our results suggested that ASP improved RA by regulating gut microbiota and gene expression, revealing a positive relationship between dietary patterns and RA.