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By Beatrice Marg-Haufe
The "first" genomics era began with the landmark Human Genome Project, which launched in 1990 and was completed in 2003, leading to the sequencing of the 20,000-25,000 human genes. It gave birth to an omics revolution and, by necessity, a series of increasingly sophisticated technologies and techniques for performing shotgun and whole genome sequencing with greater accuracy and efficiency.
The gut microbiome offers a host of opportunities for discoveries in health and disease.
Even as attention focused and refocused on characterizing the proteome, the metabolome, the immunome, and a host of other human "omes," the importance of the diverse and vast numbers of microbes that co-exist in and on the human body, their role in maintaining health and homeostasis, and their potential to cause many different types of diseases has become an area of intensive basic and translational research.
Metagenomic studies link microbiomes to disease states
The metagenomics era, although in its infancy, has already spawned a large body of literature comparing healthy microbiomes to disease states, describing innovative metagenomic strategies, and discussing the application of metagenomic data to identify novel therapeutic targets, study antibiotic resistance, and evaluate and monitor drug efficacy. Metagenomic methods, typically involving next-generation sequencing (NGS) to analyze the comprehensive genomic content of a microbial population -- comprised of bacteria, viruses, or phage -- are being applied to a range of sample types. At present, research is focusing extensively on the gut microbiome, with aberrations being linked to susceptibility to disorders such as obesity, inflammatory bowel disease (IBD), type 2 diabetes, and rheumatoid arthritis.1,2 Emerging research continues to clarify a link between the gut microbiome and the brain, with effects on sleep, stress, memory, mood and cognition.3
Relation to disease and immunity
Other metagenomic studies are zooming in on microbiomes populating the skin, respiratory tract, oral cavity and urogenital tract. They use sample types such as stool, saliva, urine or nasal swabs. An example of recent findings that link changes in the microbiome of a tissue or organ to disease are those of Lan et al. The researchers showed that the microbiome in the airways of allergic individuals differs from that of healthy persons and shares a close relationship with the type 2 inflammatory response seen in allergic airway disease.4
In addition to the importance of ongoing research aimed at profiling individual metagenomes, the value of efforts to understand the interactions and cross-talk between microbial and host genomes – between bacteria and human cells or between phage and bacteria – is becoming increasingly clear. For example, scientists at the Weizmann Institute of Science have shown that a tightly controlled regulatory network links the human immunogenome and the microbial metagenome – each regulates the other – and that aberrations in this bidirectional genetic and epigenetic control can lead to disease.5
A perfect host
Overall, the adult body is home to about 10 times more microbial cells than human cells.1 The total number of distinct genes present in the various species that comprise these microbial populations likely exceeds the number of human genes by at least two orders of magnitude.1 Furthermore, the populations comprising the gut microbiome and other microbial metagenomes can be highly dynamic, and any one study will yield only a snapshot of a particular microbiomial ecosystem. To follow changes in a microbiome over time and correlate these to homeostatic imbalance or disease manifestations requires sequential sampling and testing.
Large-scale studies to explore the human microbiome
Thus, biomedical metagenomic studies typically include large numbers of samples that continuously push the envelope for multiplexing and throughput using state-of-the-art NGS platforms and sample preparation protocols. Extending the discussion of metagenomics research beyond the focused view of human health vastly expands the scope of the field. The potential impact of metagenomics is just beginning to be realized in the environmental sciences, and in agriculture, for example, with studies underway to profile and manipulate the soil microbiome to improve crop production.
Large-scale efforts to explore the human microbiome have included the U.S. National Institutes of Health's Human Microbiome Project (HMP) and the European Commission's Metagenomics of the Human Intestinal Tract (MetaHIT) project. In 2016-2017, the White House Office of Science and Technology Policy funded a National Microbiome Initiative (NMI), in collaboration with U.S. federal agencies and private-sector stakeholders "to foster the integrated study of microbiomes across different ecosystems."
In early 2019, the Culturable Genome Reference (CGR) featuring 1,520 reference genomes from cultivated human gut bacteria was published. These reference genomes provide essential support for metagenomic analyses and functional characterization of the human gut microbiota.
Automated genomic workflows
The dramatic uptick in metagenomic research, the large sample populations and increasingly complex sequencing protocols, and the continuing and no doubt growing demand for higher throughput, reduced costs, and greater reproducibility and productivity in performing NGS is driving the need to automate genomic workflows, and especially the time- and labor-intensive steps involved in sample prep. DNA extraction and purification, quantitation and normalization, library fragment prep, and other tedious operations represent potential bottlenecks in the metagenomic workflow and are amenable to automation. In addition, automation allows for highly multiplexed sample processing prior to sequencing and tracking of sample identities throughout the process.
Tecan's Freedom EVO® workstation is a powerful tool for automating the genomics workflow. The Freedom EVO automates DNA extraction and quantification, library fragment prep, PCR set-up and other processes on one platform. Tecan works in collaboration with major research centers and NGS sample prep kit vendors -- including Illumina® and Thermo Fisher Scientific -- to develop and optimize automated NGS sample prep protocols.
Download the application note on automated Nextera® XT DNA library preparation.
- Gordon JI, Ley RE, Wilson R, et al. Extending our view of self: The human gut microbiome initiative (HGMI).
- Cho I, Blaser MJ. The human microbiome: At the interface of health and disease. Nat Rev Genet 2012;13(4):260-270.
- Galland L. The gut microbiome and the brain. J Medicinal Food 2014;17(12):1261-1272.
- Lan F, Zhang N, Gevaert E, et al. Viruses and bacteria in Th2 biased allergic airway disease. Allergy 2016;doi:10.1111/all.12934.
- Levy M, Thaiss CA, Elinav E. Metagenomic cross-talk: The regulatory interplay between immunogenomics and the microbiome. Genome Med 2015;20(7):doi:10.1186/s13073-015-0249-9.