Role of gut microbiota in the anti-rheumatoid arthritis activity of xylopic acid

The anti-rheumatoid arthritis (RA) activity of Xylopic acid (XA) was assessed in collagen-induced arthritic (CIA) mice and the role of gut microbiota was determined. Oral administration of XA resulted in decreased systemic levels of pro-inflammatory cytokines, TNF-α and NF-κB and improvement in the pathology of joints in RA mice. The 16S rRNA gene sequencing of the faecal samples of mice revealed altered microbial abundance and diversity in the arthritic mice relative to healthy mice, and treatment with XA sought to resolve this dysbiosis. Gut microbiota composition differences run through the microbial taxonomic system, from the phylum to the genus levels. In vitro anaerobic metabolism of XA by the microbiota of two human volunteers confirmed six in vivo metabolites, with three shared and the other three being unique to each volunteer. The breakdown of XA was linked to general differences in gut microbiota composition particularly the genera Faecalibacterium, Bacteroides, UCG_002, Parabacteroides, and Subdoligranulum.