Taking all studies into consideration, it was observed that the alpha diversity of the periapical microbiota consistently decreased with the progression of apical periodontitis (Figure 1D; Supplementary Figure S11) Significant differences were found in the ACE and Chao1 richness indices between healthy samples and primary apical periodontitis samples (p-values < 0.001). This evidence concerns the gene ACE and periapical periodontitis.