Conclusions and future perspectives
Although metagenomics pre-dates next-generation sequencing, current sequencing technology has transformed this emerging field, enabling the comprehensive characterization of all of the microbes in a sample. As metagenomic approaches mature and the methods are clinically validated, metagenomics-based approaches might become front-line diagnostic tests for infectious diseases in the public health setting. When faced with an unknown or complex infectious disease, multiple conventional diagnostic tests are often used, potentially leading to unnecessary costs and delays in diagnosis. Instead, metagenomics might be used as a single comprehensive screening test for potential pathogens, both known and novel, as well as to assess the state of an individual’s microbiome (Figure 2). Additional targeted diagnostic tests could then be used to further understand the clinical disease and determine management options.
As sequencing becomes cheaper and faster, it will become possible to serially characterize human microbiomes to investigate changes over time. This could lead to personalized medicine for infectious diseases that accounts for the host genome and microbiome, and to personalized treatments such as the use of narrow-spectrum antibiotics to reduce disruption of the microbiome or specific probiotics to restore an individual’s microbiome to a healthy state [82]. Similar procedures could also be applied to environmental microbiomes in healthcare settings; for example, urinary catheters could be treated with prebiotics to reduce the risk of colonization by harmful bacteria [105]. In fact, it has been suggested that metagenomic investigations of the microbiome could become so standard that DNA sequencers could be used in household toilets to monitor changes in stool microbiome content, which could then be used to guide interventions to maintain health [106].
When a pathogen of interest is known, current metagenomic approaches have limited sensitivity compared to traditional techniques for pathogen detection. Thus, although metagenomics might one day be used for screening clinical samples, it is currently best positioned as a complementary technique to be used alongside culture and other traditional methods. The greatest value of metagenomics is in clinical cases where conventional techniques fail to find a microbial cause. Even then, metagenomics requires skilled scientists to perform the experiments and to analyze the data, and thus, to date it has been exercised primarily in the realm of academic research rather than at the frontlines of public health. To be considered a bona fide clinical test for pathogen detection in a public health laboratory, standard metagenomic protocols are necessary both for testing and analyzing samples and for inter-laboratory comparison of results. As whole-genome sequencing technologies decrease in price and increase in speed and simplicity, however, it is expected that metagenomics approaches will be applied more often in public health emergencies, and routine pipelines are likely to evolve from ongoing collaborations between researchers and clinicians. Such forward steps will be crucial for increasing our arsenal of tools in public health, thus allowing us to rapidly detect and to manage novel and emerging infectious diseases.