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.
In this work, we focus on the role of the oral microbial ecosystem in periodontal disease. Periodontal disease is the most common infectious disease affecting tooth-supporting structures. Left untreated, periodontitis can lead to, or aggravate existing systemic conditions such as cardiovascular disease, diabetes, pulmonary diseases, and obesity 
. In dentistry, understanding the changes in the oral microbiome that foretell the early stages of periodontitis and dental caries, the most prevalent chronic oral diseases, may allow the better diagnosis and treatment before the appearance of the telltale clinical manifestations of these diseases (such as tissue damage in periodontal pockets or dental hard tissue loss). The emergence and evolution of antibiotic resistance in periodontal pathogens has affected the therapeutic success rates for this disease 
. New approaches are urgently needed to help regain control over periodontal disease, and microbiome studies offer a promising new angle of attack. Unraveling the complex interactions that define the oral microbiome is a fundamental, but complex component of this endeavor.
Recent developments in systems biology make it possible to perform quantitative modeling of genome-scale metabolic networks for individual microbial species 
and have been recently extended to explore small microbial consortia 
, possibly paving the way for future quantitative studies of the microbiome. However, at the ecosystem level, current modeling efforts and quantitative analyses are heavily limited by the unavailability of relevant data. Towards this goal, increasingly accessible metagenomic sequencing approaches hold the promise to enable a global systemic view of the human oral microbiome 
. Recent advances in sequencing technology are enabling scientists to generate billions of nucleotide bases at a fraction of the cost per base of traditional methods 
. This deep sequencing has revealed an unexpectedly high diversity of the human oral microbiome: dental plaque pooled from 98 healthy adults comprised about 10,000 microbial phylotypes 
- an order of magnitude higher than the previously reported 700 oral microbial phylotypes as identified by cultivation or traditional cloning and sequencing 
. The total diversity of the global oral microbiome can be estimated to be around 25,000 phylotypes 
. To date, however, we do not know how many of these microbes contribute to periodontal disease, what metabolic functions are key players in the transition from health to disease, or how common or exclusive are the oral microbiomes of unrelated healthy individuals.
Here we combine the collection of whole-community sequencing data with a number of computational analyses to provide a snapshot of the microbial component of periodontal disease at a high resolution. Specifically, we collected subgingival plaque samples from healthy and periodontally affected patients and subjected them to 16S rDNA analysis and deep sequencing in order to explore their microbiome. Our analyses reveal a number of trends in genomic diversity and biological function enrichment during disease that allow us to formulate a novel hypothesis on the nature of periodontal disease. We also demonstrate the power of high-throughput sequencing approaches by reconstructing an unculturable member of the TM7 group, complementing an initial analysis that relied on single cell genomic approaches. We also characterize several regions of variation within one of the dominant members of the oral cavity, Actinomyces naeslundii. This paper describes a genomic and metabolic examination of the differences between the healthy and diseased periodontal microbiome.