This study defines the healthy "core microbiome" of the oral microbial communities using 454 pyrosequencing technology. Researchers analyzed microbiomes from several intraoral niches in three healthy individuals, identifying over 3600 unique sequences, over 500 OTUs (species-level phylotypes), and 88-104 higher taxa. The predominant taxa included Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteria. Each individual sample contained an average of 266 species-level phylotypes, with cheek samples being the least diverse and dental samples from approximal surfaces showing the highest diversity. Principal component analysis distinguished samples from shedding surfaces (mucosa of tongue, cheek, and palate) from those from solid surfaces (teeth). There was significant overlap in higher taxa, species-level phylotypes, and unique sequences among the three microbiomes, with 84% of higher taxa, 75% of OTUs, and 65% of unique sequences present in at least two microbiomes. The three individuals shared 1660 of 6315 unique sequences, which contributed 66% of the reads. The overlapping OTUs contributed to 94% of the reads, while nearly all reads (99.8%) belonged to the shared higher taxa. The study provides the first insight into the diversity and uniqueness of individual oral microbiomes at a resolution of next-generation sequencing, supporting the concept of a core microbiome at health. The results suggest that a major proportion of bacterial sequences of unrelated healthy individuals is identical, indicating a core microbiome. The study also highlights the importance of considering site specificity in future research designs, as the oral microbiome varies between mucosal and dental sites, and between saliva and dental sites. The findings have implications for understanding the oral microbiome's role in health and disease, and could inform future diagnostic and treatment strategies.This study defines the healthy "core microbiome" of the oral microbial communities using 454 pyrosequencing technology. Researchers analyzed microbiomes from several intraoral niches in three healthy individuals, identifying over 3600 unique sequences, over 500 OTUs (species-level phylotypes), and 88-104 higher taxa. The predominant taxa included Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteria. Each individual sample contained an average of 266 species-level phylotypes, with cheek samples being the least diverse and dental samples from approximal surfaces showing the highest diversity. Principal component analysis distinguished samples from shedding surfaces (mucosa of tongue, cheek, and palate) from those from solid surfaces (teeth). There was significant overlap in higher taxa, species-level phylotypes, and unique sequences among the three microbiomes, with 84% of higher taxa, 75% of OTUs, and 65% of unique sequences present in at least two microbiomes. The three individuals shared 1660 of 6315 unique sequences, which contributed 66% of the reads. The overlapping OTUs contributed to 94% of the reads, while nearly all reads (99.8%) belonged to the shared higher taxa. The study provides the first insight into the diversity and uniqueness of individual oral microbiomes at a resolution of next-generation sequencing, supporting the concept of a core microbiome at health. The results suggest that a major proportion of bacterial sequences of unrelated healthy individuals is identical, indicating a core microbiome. The study also highlights the importance of considering site specificity in future research designs, as the oral microbiome varies between mucosal and dental sites, and between saliva and dental sites. The findings have implications for understanding the oral microbiome's role in health and disease, and could inform future diagnostic and treatment strategies.