Microbiome in health and disease
Microbiome

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Friend or foe: Metagenomics in health and disease

Human bodies are colonized by trillions upon trillions of microbes, including bacteria, archaea, fungi, protists and viruses. These organisms are collectively termed the microbiota, with their numbers relative to the number of human cells ranging from a low estimate of a 1:1 ratio to a high estimate of 10:1. The human microbiota is incredibly diverse, with microbial populations present in a multitude of different tissues, systems, regions, and fluids. Of these, the two best characterized and most well-known populations are arguably the oral and gut microbiotas, both of which have been revealed to be crucial to homeostasis and pathogenesis.

The microbiota of the oral cavity stands apart from other region-specific microbiotas in that it facilitates pathogenesis (dental caries and periodontal diseases) under normal circumstances, thus resulting in the necessity of oral hygiene practices. At the same time, the mere presence of the oral microbiota passively inhibits colonization by pathogens, with several resident species revealed to exert direct antipathogen effects (1). Investigating the oral microbiota through characterization of the oral microbiome is naturally challenging, given that the oral microbiota is comprised of at least 700 microbial species (2). Further, the oral cavity is constantly exposed to external environments and microbial milieus, whether through food consumption, air intake or social contact (e.g., kissing) (1).

Microbial DNA
The first metagenomic profiles of the oral microbiome focused on oral diseases, revealing distinct and complex multispecies microbial communities within dental plaques and caries.

This complexity makes it extremely difficult to pinpoint specific pathological agents and/or mechanisms using traditional methods such as bacterial culture. However, metagenomics, in tandem with the advent of next-generation sequencing technology, is now capable of studying entire microbial communities at the same time (3). The first metagenomic profiles of the oral microbiome focused on oral diseases, revealing both the distinct and complex multispecies microbial communities within dental plaques and caries, as well as stark differences in microbiota composition between individuals who suffered from these conditions versus those who did not (3, 4). Further studies have used metagenomics approaches to further expand upon the latter, helping to construct bacterial profiles characteristic of individuals with periodontal or other inflammatory diseases (2). This is especially relevant given that oral inflammation has been linked to elevated risk of cardiovascular disease (5). Indeed, metagenomics has been used to find that bacteria in atherosclerotic plaques are also present in similar abundances in the oral cavity, indicating both a potential relationship between the two populations and the possibility that the oral microbiome could be used as a biomarker for cardiovascular disease (6).


The gut microbiota

The gut microbiota is the most widely known human-resident microbial community. While typically dominated by only two phyla, the gut microbiota is immensely diverse at lower taxonomic levels. Indeed, as of 2016, over 10 million genes have been identified and cataloged to comprise the gut microbiome (7). In the same way that the oral microbiota is partially shaped by external contacts, the composition of the gut microbiota is modulated by long-term dietary habits (7). Given its role in digestion and metabolism, it is unsurprising that the gut microbiota has been linked to obesity and metabolic diseases such as type II diabetes (7). Metagenomic approaches have been used to investigate gut microbiome properties in efforts to identify specific markers and/or profiles associated with pathology (8). Studies in lean and obese individuals, for example, have found that the latter group can exhibit greater species diversity and/or experience proportional shifts in microbiome composition (9), while metagenomic profiling of gut microbiota from diabetic patients have identified species-specific polymorphism biomarkers (10–11).

Metagenomic approaches have been used to investigate gut microbiome properties in efforts to identify specific markers and/or profiles associated with pathology.
 
Similar approaches have also been used in attempts to examine the role of the microbiota in inflammatory bowel diseases (IBDs), finding key differences in composition and transcriptional activity in the genomes and transcriptomes of microbiota from patients suffering from IBDs (12). Finally, the microbiota can contain oncogenic microbes such as Helicobacter pylori and the human papillomavirus (HPV). To this end, researchers are probing any possible relationship between the microbiota and cancer, with metagenomic analyses identifying changes in microbiome composition in a variety of cancers, including colorectal, breast and gastric cancers (13–15).

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References
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  2. Xu, P. and Gunsolley, J. (2014) Application of metagenomics in understanding oral health and disease. Virulence 5(3), 424–432.
  3. Belda-Ferre, P. et al. (2012) The oral metagenome in health and disease. ISME J. 6(1), 46–56.
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  11. Chen, Y. (2017) Gut metagenomes of type 2 diabetic patients have characteristic single-nucleotide polymorphism distribution in Bacteroides coprocola. Microbiome 5, 15.
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