Understanding the role of microbial communities in human health is emerging as one of the most important and fascinating biomedical challenges of our times. Our body harbors an enormous amount of microbial cells, estimated to exceed the number of human cells by an order of magnitude. These microbes are organized into complex communities specifically adapted to inhabit different niches of the human body, such as the skin, and the respiratory, gastrointestinal, and urogenital tracts. Such ecosystems carry a broad range of functions indispensable for the wellbeing of the host. At the same time, the rise of pathogens within such communities, causing infection and inflammation, constitutes an ongoing challenge in biomedical research. This is especially true in light of the slow rate at which new antibiotics are discovered, and the increase in the number of microbes that can resist treatment.
In contrast to the traditional view of individual pathogens being responsible for disease onset, recent microbial ecosystem diversity analyses seem to point to a new perspective in which the transition from health to disease is attributed to a shift in the global balance of the microbial flora rather than to the specific appearance of individual pathogens. However, the mechanisms that underlie the connection between disease or infection and the dynamics of the host-associated ecosystems are still poorly understood. This paper focuses on the role of the oral microbial ecosystem in periodontal disease, the most common infectious disease affecting tooth-supporting structures.
Deep Sequencing of the Oral Microbiome Reveals Signatures of Periodontal Disease. (2012) PLoS ONE 7(6): e37919. 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.