Methotrexate regimen and periodontal therapy change the oral-gut microbiota composition in rheumatoid arthritis

Abstract Objectives This study evaluated the influence of methotrexate (MTX) and periodontal therapy on the composition of the oral-gut microbiota of individuals with RA. Methods Thirty-seven individuals with RA were evaluated at three time points. The composition of the oral and gut microbiota was assessed by amplifying the V4 region of the 16S gene from subgingival plaques and stools. Results MTX tended to reduce the alpha diversity of the oral and gut microbiota, an effect that was partially reversed in the oral microbiota after periodontal treatment. The relative abundance of the oral microbiota was directly influenced by periodontal status. Conversely, periodontitis did not influence the gut microbiota. MTX treatment did not affect the periodontal condition; however, it modified the interactions between clinical parameters and the oral-gut microbiota, with the emergence of novel and simplified correlations. Porphyromonas gingivalis was linked to increased production of neutrophil extracellular traps (NET) regardless of periodontal status and this periodontopathogenic bacterium induced significant production of NET in vitro, particularly in individuals with RA. Conclusion MTX and periodontal treatment directly affected the composition and richness of the oral-gut microbiota, with the emergence of different microbial groups. P. gingivalis and NET typify the microbial-host interaction in RA and periodontitis.