MicrobiologyBytes

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.

Bifidobacteria are relatively abundant inhabitants of the gastrointestinal tract of humans and animals. Many bifidobacterial species, in conjunction with other members of the intestinal microbiota are believed to contribute to host nutrition, while also impacting on intestinal pH, cell proliferation and differentiation, development and activity of the immune system, and innate and acquired responses to pathogens. These perceived beneficial health effects have driven commercial exploitation of bifidobacteria as live components of many functional foods and therapeutic adjuncts. However, bifidobacteria have also been isolated from the human oral cavity, where their presence is linked to the progression of tooth decay: bifidobacteria have been detected in high numbers in infected dentine from carious lesions in children and have been associated with childhood dental caries. can be found as part of the microbiota implicated in human dental caries. In recent surveys of oral bifidobacteria associated with caries in adults and children and root caries in adults, Bifidobacterium dentium was the most frequently isolated Bifidobacterium species, representing approximately eight percent of the culturable bacteria isolated from active lesions. This species is capable of acidogenesis to produce a final pH in glucose-containing media below pH 4.2, sufficient to cause extensive demineralisation of tooth tissues. B. dentium may therefore significantly contribute to the pathogenesis of dental caries which is one of the most common chronic diseases, remaining untreated in many underdeveloped countries where dental pain is often alleviated only by the loss or extraction of the affected tooth.

Researchers have now uncovered the complete genetic make-up of the cavity-causing bacterium B. dentium Bd1, revealing the genetic adaptations that allow this microorganism to live and cause decay in the human oral cavity. Bifidobacteria, largely known as long-term beneficial gut bacteria, are often included as probiotic components of food to aid digestion and boost the immune system. However, not all species within the genus Bifidobacterium provide beneficial effects to the host’s health. In fact, B. dentium is an opportunistic pathogen since it has been linked to the development of tooth decay. The genome sequence of B. dentium Bd1 reveals how this microorganism has adapted to the oral environment through specialized nutrient acquisition features, acid tolerance, defences against antimicrobial substances and other gene products that increase fitness and competitiveness within the oral niche. This report identifies, through various genomic approaches, specific adaptations of a Bifidobacterium taxon to a lifestyle as a tooth decay-causing bacterium. The data in this study indicate that the genome of this opportunistic pathogen has evolved through only a small number of horizontal gene acquisition events, highlighting the narrow boundary that separates bacteria that are long-term residents on or in the human body from opportunistic pathogens.

The Bifidobacterium dentium Bd1 Genome Sequence Reflects Its Genetic Adaptation to the Human Oral Cavity. 2009 PLoS Genet 5(12): e1000785. doi:10.1371/journal.pgen.1000785
Bifidobacteria, one of the relatively dominant components of the human intestinal microbiota, are considered one of the key groups of beneficial intestinal bacteria (probiotic bacteria). However, in addition to health-promoting taxa, the genus Bifidobacterium also includes Bifidobacterium dentium, an opportunistic cariogenic pathogen. The genetic basis for the ability of B. dentium to survive in the oral cavity and contribute to caries development is not understood. The genome of B. dentium Bd1, a strain isolated from dental caries, was sequenced to completion to uncover a single circular 2,636,368 base pair chromosome with 2,143 predicted open reading frames. Annotation of the genome sequence revealed multiple ways in which B. dentium has adapted to the oral environment through specialized nutrient acquisition, defences against antimicrobials, and gene products that increase fitness and competitiveness within the oral niche. B. dentium Bd1 was shown to metabolize a wide variety of carbohydrates, consistent with genome-based predictions, while colonization and persistence factors implicated in tissue adhesion, acid tolerance, and the metabolism of human saliva-derived compounds were also identified. Global transcriptome analysis demonstrated that many of the genes encoding these predicted traits are highly expressed under relevant physiological conditions. This is the first report to identify, through various genomic approaches, specific genetic adaptations of a Bifidobacterium taxon, Bifidobacterium dentium Bd1, to a lifestyle as a cariogenic microorganism in the oral cavity. In silico analysis and comparative genomic hybridization experiments clearly reveal a high level of genome conservation among various B. dentium strains. The data indicate that the genome of this opportunistic cariogen has evolved through a very limited number of horizontal gene acquisition events.