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Deep sequencing of the oral microbiome reveals signatures of periodontal disease.

Liu B, Faller LL, Klitgord N, Mazumdar V, Ghodsi M, Sommer DD, Gibbons TR, Treangen TJ, Chang YC, Li S, Stine OC, Hasturk H, Kasif S, Segrè D, Pop M, Amar S - PLoS ONE (2012)

Bottom Line: While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood.Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome.Despite a modest level of sequencing (~2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ~90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes.

View Article: PubMed Central - PubMed

Affiliation: Center for Bioinformatics and Computational Biology, University of Maryland, College Park, Maryland, United States of America.

ABSTRACT
The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (~2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ~90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes.

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Schematic representation of the putative metabolic lifestyle shifts associated with the change in microbial flora around the tooth and gum tissue upon the transition from a healthy (A) to an advanced periodontal disease (B) state.The healthy state is dominated by the bacterial genera Streptococcus, Fusobacterium, Actinomyces, and Corynebacterium, whereas the disease state is primarily dominated by pathogenic genera such as Prevotella, Leptotrichia, Treponema, and Fusobacterium.
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pone-0037919-g004: Schematic representation of the putative metabolic lifestyle shifts associated with the change in microbial flora around the tooth and gum tissue upon the transition from a healthy (A) to an advanced periodontal disease (B) state.The healthy state is dominated by the bacterial genera Streptococcus, Fusobacterium, Actinomyces, and Corynebacterium, whereas the disease state is primarily dominated by pathogenic genera such as Prevotella, Leptotrichia, Treponema, and Fusobacterium.

Mentions: Combined with the metabolic analyses described above, these results suggest that some systems-level changes may be associated with periodontal disease and the transition between health and disease. Microbial consortia in healthy individuals (Figure 4A) may rely on a highly diverse and rapidly changing supply of nutrients, as well as on good availability of oxygen for respiration. The relative paucity of enriched pathways in our healthy case analysis may reflect the diversity of metabolic pathways represented in the community. This is also supported by the clustering analysis of 16S rDNA data (Figure 3B) and of enzyme frequency data (Figure 3C), which show that the healthy data points do not tend to cluster together (Figure 4A, bottom left inset), and is consistent with a community with a lower taxonomic diversity (Figure 3A). On the contrary, the metabolic functions present in the microbial flora associated with periodontal disease (Figure 4B) seem to display a significant enrichment in specific metabolic pathways, compatible with an oxygen poor environment [50], and the availability of amino acids and lipids as major carbon sources. This may reflect the invasion of microbial pathogens (e.g. Prevotella intermedia which is enriched in the diseased samples) into human cells (both epithelial cells and macrophages). The disease flora is rich in lipid degradation pathways, as well as other known virulence-related activities, such as LPS biosynthesis. In turn, the consistency of the intracellular environment across different patients may explain why the disease points tend to cluster together in the Principal Component Analysis (PCA) plots. The ensuing picture is that the disease state is an attractor in the space of metabolic functions, with enrichment in cytotoxic and parasitic functions.


Deep sequencing of the oral microbiome reveals signatures of periodontal disease.

Liu B, Faller LL, Klitgord N, Mazumdar V, Ghodsi M, Sommer DD, Gibbons TR, Treangen TJ, Chang YC, Li S, Stine OC, Hasturk H, Kasif S, Segrè D, Pop M, Amar S - PLoS ONE (2012)

Schematic representation of the putative metabolic lifestyle shifts associated with the change in microbial flora around the tooth and gum tissue upon the transition from a healthy (A) to an advanced periodontal disease (B) state.The healthy state is dominated by the bacterial genera Streptococcus, Fusobacterium, Actinomyces, and Corynebacterium, whereas the disease state is primarily dominated by pathogenic genera such as Prevotella, Leptotrichia, Treponema, and Fusobacterium.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3366996&req=5

pone-0037919-g004: Schematic representation of the putative metabolic lifestyle shifts associated with the change in microbial flora around the tooth and gum tissue upon the transition from a healthy (A) to an advanced periodontal disease (B) state.The healthy state is dominated by the bacterial genera Streptococcus, Fusobacterium, Actinomyces, and Corynebacterium, whereas the disease state is primarily dominated by pathogenic genera such as Prevotella, Leptotrichia, Treponema, and Fusobacterium.
Mentions: Combined with the metabolic analyses described above, these results suggest that some systems-level changes may be associated with periodontal disease and the transition between health and disease. Microbial consortia in healthy individuals (Figure 4A) may rely on a highly diverse and rapidly changing supply of nutrients, as well as on good availability of oxygen for respiration. The relative paucity of enriched pathways in our healthy case analysis may reflect the diversity of metabolic pathways represented in the community. This is also supported by the clustering analysis of 16S rDNA data (Figure 3B) and of enzyme frequency data (Figure 3C), which show that the healthy data points do not tend to cluster together (Figure 4A, bottom left inset), and is consistent with a community with a lower taxonomic diversity (Figure 3A). On the contrary, the metabolic functions present in the microbial flora associated with periodontal disease (Figure 4B) seem to display a significant enrichment in specific metabolic pathways, compatible with an oxygen poor environment [50], and the availability of amino acids and lipids as major carbon sources. This may reflect the invasion of microbial pathogens (e.g. Prevotella intermedia which is enriched in the diseased samples) into human cells (both epithelial cells and macrophages). The disease flora is rich in lipid degradation pathways, as well as other known virulence-related activities, such as LPS biosynthesis. In turn, the consistency of the intracellular environment across different patients may explain why the disease points tend to cluster together in the Principal Component Analysis (PCA) plots. The ensuing picture is that the disease state is an attractor in the space of metabolic functions, with enrichment in cytotoxic and parasitic functions.

Bottom Line: While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood.Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome.Despite a modest level of sequencing (~2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ~90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes.

View Article: PubMed Central - PubMed

Affiliation: Center for Bioinformatics and Computational Biology, University of Maryland, College Park, Maryland, United States of America.

ABSTRACT
The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (~2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ~90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes.

Show MeSH
Related in: MedlinePlus