Therefore, we developed a co-culture model of P. gingivalis and F. nucleatum to evaluate whether the activation of the TLR4 pathway is enhanced, thus augmenting the expressions of pro-inflammatory mediators and cell migration, both processes that are directly related to the progression of periodontitis [16,26,28,30,31] and are linked to the onset of oral cancer [27,29,62,63,64,65]. This evidence concerns the gene TLR4 and periodontitis.