Secondly, as an observational study, our study only demonstrated the relationship of gut microbiotas and their metabolites with Tfr cells in RA instead of the causality, it is necessary to conduct the vitro experiments to elucidate the causal relationship between them and identify whether the gut microbiotas and their metabolites contribute to the pathogenesis of RA by influencing Tfr cells as one of the mechanisms involved in the gut-joint axis. This evidence concerns the gene TFRC and rheumatoid arthritis.