The oral cavity is richly populated with polymicrobial communities. Bacteria associated with the oral cavity are associated with a number of diseases, such as periodontal disease, dental caries and endodontic infections. Moreover, bacteria from this environment have also been implicated in diseases elsewhere in the body, including cardiovascular disease, cancer and rheumatoid arthritis. The tipping point in the balance between health and disease in human microbiomics is still unclear. Using next -generation sequencing, we investigated the bacterial content in endodontic lesions obtained by means of apical surgery. Our findings indicate that these lesions are populated with a complex mixture of bacteria that are dominated by periodontal pathogens, most notably Fusobacterium, Prevotella and Porphyromonas. We also investigated the bacterial environment in periodontal pockets, monitoring the changes that occur from standard treatment. This was done using the bacterial 16S ribosomal RNA marker gene as well as whole-genome shotgun sequencing for metagenomics analyses on a subset of these samples. Our 16S study found changes in the abundance of some taxa in individuals whose condition improved with treatment. However, samples before and after treatment from the same individuals were most consistently similar to each other. Phylogenetic analyses of the periodontal pathogens Prevotella and Fusobacterium from these samples uncovered unexpected diversity and varied response to treatment amongst different species. Based on these findings, we hypothesize that differences in interpersonal microbiomes have an effect on the response to treatment. Metagenomics analyses enabled us to better characterize the overall environment of a subset of the samples. Our taxonomic identification results are comparable with those from the 16S study with 19 identical genera in the top 25 genera identified in this subset. Two genera identified by metagenomics were not present in the 16S data at all: Haemophilus and Eikenella. In functional gene categories, we saw an increase in virulence factors after treatment. We hypothesize that a longer period of time needs to pass after treatment before drawing more conclusions, allowing the bacteria time to reach a new steady state after perturbation