Oleanolic acid ameliorates collagen induced arthritis in rats through the gut microbiota.

OBJECTIVES: Oleanolic acid (OA) is a natural anti-inflammatory triterpenoid. This study investigates its therapeutic potential against rheumatoid arthritis (RA), a chronic autoimmune condition characterized by inflammatory activity, and explores the novel mechanism of gut microbiota modulation in a rat model. METHODS: The anti-arthritic effect of OA was assessed in collagen-induced arthritis (CIA) in rats following oral or intravenous administration. Arthritis severity, joint pathology, and mesenteric Th17/Treg cell frequencies were evaluated. The role of gut microbiota was investigated using 16S rRNA sequencing and antibiotic ablation. KEY FINDINGS: Oral, but not intravenous, OA administration significantly alleviated arthritis and joint damage in CIA rats, indicating a gastrointestinal-dependent mechanism. Therapeutically, oral OA modulated gut microbiota by reducing Prevotella abundance and restored immune balance by decreasing Th17 and increasing Treg cell frequencies. This protective effect was abolished by co-treatment with antibiotics, confirming gut microbiota-dependency. CONCLUSIONS: Taken together, our findings show that the improvement in CIA after oral administration of OA is mainly due to changes in the structure and function of the gut microbiota. This study, therefore, suggests that OA is a promising therapeutic candidate for RA, based on its ability to restore the intestinal microenvironment.