Deep sequencing of the oral microbiome reveals signatures of periodontal disease

• Published in: PloS one 2012-06, Vol.7 (6), p.e37919
• Main Authors: Liu, Bo, Faller, Lina L, Klitgord, Niels, Mazumdar, Varun, Ghodsi, Mohammad, Sommer, Daniel D, Gibbons, Theodore R, Treangen, Todd J, Chang, Yi-Chien, Li, Shan, Stine, O Colin, Hasturk, Hatice, Kasif, Simon, Segrè, Daniel, Pop, Mihai, Amar, Salomon
• Format: Article
• Language: English
• Subjects: Acids; Actinomyces - drug effects; Actinomyces - genetics; Adult; Antibiotics; Bacteria; Bioinformatics; Biology; Biomedical engineering; Cardiovascular diseases; Computer Science; Contamination; Deoxyribonucleic acid; Disease; DNA; DNA sequencing; Drug resistance; Drug Resistance, Bacterial - drug effects; Drug Resistance, Bacterial - genetics; E coli; Ecosystem biology; Ecosystems; Encyclopedias; Environmental changes; Epidemiology; Gene Expression Profiling; Gene sequencing; Genes; Genes, Bacterial - genetics; Genetic Variation - drug effects; Genetic Variation - genetics; Genomes; Genomics; Gum disease; Health; Health risks; High-Throughput Nucleotide Sequencing - methods; Homeostasis; Humans; Markov analysis; Medicine; Metabolic Networks and Pathways - drug effects; Metabolic Networks and Pathways - genetics; Metabolism; Metagenome - drug effects; Metagenome - genetics; Metagenomics; Metals - pharmacology; Middle Aged; Mouth - drug effects; Mouth - microbiology; Next-generation sequencing; Parasitic diseases; Pathogenesis; Paths; Periodontal disease; Periodontal diseases; Periodontal Diseases - genetics; Periodontal Diseases - microbiology; Periodontitis; Periodontitis - genetics; Periodontitis - microbiology; Public health; Reference Standards; Risk factors; RNA; RNA, Ribosomal, 16S - genetics; rRNA 16S; Taxonomy; Trends; Virulence; Virulence (Microbiology); Virulence factors; Virulence Factors - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0037919

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.