Arsenic trioxide modulates the composition and metabolic function of the gut microbiota in a mouse model of rheumatoid arthritis

The mechanism of rheumatoid arthritis (RA) has been widely investigated, and studies on the use of arsenic trioxide (ATO) in the treatment of RA have been reported in recent years. However, the exact mechanism of action of ATO in RA remains unclear. This study explores alterations in the gut microbiota and metabolism during ATO treatment in a mouse model of RA and provides an integrative analysis of the biomechanism. The purpose of this study was to verify whether ATO can alleviate RA by altering the gut microbiota. In this study, the mice were randomly divided into four different groups: the normal control (NC) group, the collagen-induced arthritis (CIA) group, the ATO 1.0 mg/kg/day group, and the ATO 2.0 mg/kg/day group. Fecal samples were collected. Through 16S rDNA gene sequencing and metabolomic analysis, the effect of ATO on the composition and metabolites of gut microbiota in CIA mice was investigated. The results showed that compared with NC mice, CIA mice showed differences at both the phylum level (Firmicutes and Bacteroidetes) and the genus level (Muribaculaceae_unclassified and Alistipes). Meanwhile, many metabolites were significantly changed between the two groups, including benzoic acid and (s)-2-acetolactate. However, these alterations were partially reversed in ATO-treated CIA mice. These results indicated that ATO treatment modulated gut microbiota disorder and improved fecal metabolite abnormalities. In conclusion, this study provided important evidence for alterations of the gut microbiota and metabolites and the role of these alterations in a potential novel mechanism of ATO treatment in RA.