Background: Rheumatoid arthritis (RA) is a chronic inflammatory disabling autoimmune disorder. Little is known regarding the association between the gut microbiome and etiopathogenesis of RA. We aimed to dissect the differences in gut microbiomes associated with RA in comparison to healthy individuals and, in addition, to identify the shifts in the bacterial community in association with disease activity; Methods: In order to identify compositional shifts in gut microbiomes of RA patients, V3-V4 hypervariable regions of 16S rRNA were sequenced using Illumina MiSeq. In total, sixty stool samples were collected from 45 patients with RA besides 15 matched healthy subjects; Results: Notably, RA microbiomes were significantly associated with diverse bacterial communities compared with healthy individuals. Likewise, a direct association between bacterial diversity and disease activity was detected in RA patients (Kruskal Wallis; p = 0.00047). In general, genus-level analysis revealed a positive coexistence between RA and Megasphaera, Adlercreutzia, Ruminococcus, Bacteroides, Collinsella, and Acidaminococcus. Furthermore, Spearman correlation analysis significantly stratified the most dominant genera into distinct clusters that were mainly based on disease activity (r ≥ 0.6; p ≤ 0.05). The predictive metabolic profile of bacterial communities associated with RA could support the potential impact of gut microbiomes in either the development or recovery of RA; Conclusions: The overall shifts in bacterial composition at different disease statuses could confirm the cross-linking of certain genera either to causation or progression of RA.