Abstract
The bacteria, fungi, and viruses that live on and in us have a tremendous impact on our day-to-day health and are often linked to many diseases, including autoimmune disorders and infections. Diagnosing and treating these disorders relies on accurate identification and characterization of the microbial community. Current sequencing technologies allow the sequencing of the entire nucleic acid complement of a sample providing an accurate snapshot of the community members present in addition to the full genetic potential of that microbial community. There are a number of clinical applications that stand to benefit from these data sets, such as the rapid identification of pathogens present in a sample. Other applications include the identification of antibiotic-resistance genes, diagnosis and treatment of gastrointestinal disorders, and many other diseases associated with bacterial, viral, and fungal microbiomes. Metagenomics also allows the physician to probe more complex phenotypes such as microbial dysbiosis with intestinal disorders and disruptions of the skin microbiome that may be associated with skin disorders. Many of these disorders are not associated with a single pathogen but emerge as a result of complex ecological interactions within microbiota. Currently, we understand very little about these complex phenotypes, yet clearly they are important and in some cases, as with fecal microbiota transplants in Clostridium difficile infections, treating the microbiome of the patient is effective. Here, we give an overview of metagenomics and discuss a number of areas where metagenomics is applicable in the clinic, and progress being made in these areas. This includes (1) the identification of unknown pathogens, and those pathogens particularly hard to culture, (2) utilizing functional information and gene content to understand complex infections such as Clostridium difficile, and (3) predicting antimicrobial resistance of the community using genetic determinants of resistance identified from the sequencing data. All of these applications rely on sophisticated computational tools, and we also discuss the importance of skilled bioinformatic support for the implementation and use of metagenomics in the clinic.
Highlights
The complement of microorganisms that live on and within us, our microbiome, and its role in health and disease has become a central focus of current research
We discuss how this information is useful in a clinical context for both diagnostics and research with a particular emphasis on complex microbiomeassociated phenotypes such as dysbiosis and Clostridium difficile infection
In addition to infection diagnostics, metagenomics has a great deal of potential for unraveling the microbial ecology of complicated disorders such as Clostridium difficile infection (CDI)
Summary
The complement of microorganisms that live on and within us, our microbiome, and its role in health and disease has become a central focus of current research. Shotgun sequencing of purified DNA, or metagenomics, is rapidly emerging as a powerful tool for both microbiology research and clinical applications due to the depth and breadth of information that can be acquired. The volume of DNA sequencing required to fully sequence a sample such as the human gut microbiome has traditionally made routine metagenomics unfeasible, for diagnostics. We discuss how this information is useful in a clinical context for both diagnostics and research with a particular emphasis on complex microbiomeassociated phenotypes such as dysbiosis and Clostridium difficile infection. As sequencing technology continues to evolve rapidly, the most significant bottleneck for metagenomics (and other genomic analysis, for that matter) will not be sequencing, but the presence of skilled analysts to analyze the data and tease out the clinically relevant information is required
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