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Periodontitis is a common condition characterized by an exacerbated pro-inflammatory response, which leads to tissue destruction and, ultimately, alveolar bone loss. In this pilot study, we assess the microbiota composition and cytokine profile changes in patients with stage III/IV, grade B/C periodontitis, specifically by comparing healthy and diseased sites in the same oral cavity. Overall, we found that microbiota architecture was significantly disrupted between diseased and healthy sites, and that the clustering was driven, in part, by the increased relative abundances of Synergistetes in diseased sites, as well as the increased abundances of Firmicutes in healthy sites. We also observed that diseased sites were enriched in Synergistetes, TM7, SR1, Spirochaetes, Bacteroidetes and Fusobacteria, and depleted in Firmicutes, Proteobacteria, Tenericutes and Actinobacteria compared to healthy sites. We found that Interleukin-1b, Interleukin-4, Interleukin-10, and Interleukin-17A were significantly overexpressed in diseased sites, whereas Interleukin-6 and TNF-alpha do not differ significantly between healthy and diseased sites. Here, we observed concomitant changes in the subgingival plaque microbiota and cytokines profile, suggesting that this combined alteration could contribute to the pathobiology of periodontitis. [ABSTRACT FROM AUTHOR]