Comparative analysis of the treatment-naive microbiome across rheumatic diseases to predict MTX treatment response

The human gut microbiota is recognized as a modulator of inflammatory diseases and has been linked to interindividual differences in therapy responsiveness. However, the robustness of disease-specific microbiome signatures across closely related diseases is rarely compared. Here, we compared treatment-naive microbiota composition and functional potential across rheumatic diseases, including rheumatoid arthritis (RA) and spondyloarthritis subforms, to identify disease-specific biomarkers. While we failed to define robust disease-specific microbiota signatures, we identified microbial signatures linked to methotrexate (MTX) responsiveness for the two rheumatic diseases RA and psoriatic arthritis (PsA), for which MTX is the first-line treatment. Notably, the signatures were distinct, i.e., we could define a signature based on the relative abundance of microbial species for RA, yet the signature for PsA was based on the relative abundance of microbial pathways. Together this supports the previously recognized value of microbiota to predict treatment responses to MTX in RA and identifies distinct signatures predicting MTX responsiveness for PsA.