Some science behind the scenes

Metagenomic testing

Metagenomics is the study of genetic material recovered directly from environmental samples. Whilst traditional microbiology and microbial genome sequencing and genomics rely upon cultivated clonal cultures, early environmental gene sequencing cloned specific genes to produce a profile of diversity in a natural sample. In other words, there is no need to guess what microbes exist in a sample and then culture them to prove the point, the test reveals all the microbes present.

Such tests have already revealed that the vast majority of microbial biodiversity has been missed by cultivation-based methods.  Because of its ability to reveal the previously hidden diversity of microscopic life, metagenomics offers a powerful method for viewing the microbial world previously denied to the researcher, research that “has the potential to revolutionize understanding of the entire living world.”

One of the two applications that are of especial interest to this site are the diagnosis of illness and the mapping of the intestinal flora.

Diagnosing illness

Differentiating between infectious and non-infectious illness, and identifying the underlying etiology of infection, can be quite challenging. For example, more than half of cases of encephalitis remain undiagnosed, despite extensive testing using state-of-the-art clinical laboratory methods.

Metagenomic sequencing shows promise as a sensitive and rapid method to diagnose infection by comparing genetic material found in a patient's sample to a database of thousands of bacteria, viruses, fungi, parasites and other pathogens.  As we can see from the observation, it is already being done, this is but one example.

Gut Microbe Characterization

Metagenomic sequencing is being used to characterize the microbial communities from 15-18 body sites from at least 250 individuals. This is part of the Human Microbiome initiative with primary goals to determine if there is a core human microbiome, to understand the changes in the human microbiome that can be correlated with human health, and to develop new technological and bioinformatics tools to support these goals.

Another medical study as part of the MetaHit (Metagenomics of the Human Intestinal Tract) project consisted of 124 individuals from Denmark and Spain consisting of healthy, overweight, and irritable bowel disease patients. The study attempted to categorize the depth and phylogenetic diversity of gastrointestinal bacteria. The study demonstrated that two bacterial divisions, Bacteroidetes and Firmicutes, constitute over 90% of the known phylogenetic categories that dominate distal gut bacteria. Using the relative gene frequencies found within the gut these researchers identified 1,244 metagenomic clusters that are critically important for the health of the intestinal tract.

There are two types of functions in these range clusters: housekeeping and those specific to the intestine. The housekeeping gene clusters are required in all bacteria and are often major players in the main metabolic pathways including central carbon metabolism and amino acid synthesis. The gut-specific functions include adhesion to host proteins and the harvesting of sugars from globoseries glycolipids. Patients with irritable bowel syndrome were shown to exhibit 25% fewer genes and lower bacterial diversity than individuals not suffering from irritable bowel syndrome indicating that changes in patients’ gut biome diversity may be associated with this condition.

While these studies highlight some potentially valuable medical applications, only 31-48.8% of the reads could be aligned to 194 public human gut bacterial genomes and 7.6-21.2% to bacterial genomes available in GenBank which indicates that there is still far more research necessary to capture novel bacterial genomes.


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