Metagenomics: Unveiling hidden life

Stefanie Vogt
12 June 2015

Above: Image ©

Did you know? Scientists have found differences in the gut microbes of lean and obese humans, suggesting that changes in gut bacteria may be contributing to the obesity epidemic.Humans like to think of themselves as a hardy species. For thousands of years, we have survived in challenging environments from arctic tundra to tropical jungles. While that’s pretty impressive, we’ve got nothing on microbes. Microbes can be found in virtually every environment on Earth, including those that seem completely uninhabitable from a human perspective.

Even though microbes can handle extreme conditions, scientists still don’t know how to grow many of them. So well adapted to the environments they normally call home, only a small fraction of bacteria have been successfully grown in a lab. So how can researchers study these microbes if they can’t even grow them? The answer lies in a new area of research in the field of genomics, called metagenomics.

Metagenomics is the study of DNA sequenced directly from any environment where microbes can be found, anywhere from the ocean floor to a wheel of cheese. By skipping the step of growing microbes in the lab and looking directly at their DNA, scientists can get a clearer view of which microbes are present in a particular environment. This approach to studying microbes has gained popularity in recent years, as DNA sequencing has become faster and less expensive.

What's left to explore?

Nathan Wolfe, TED

In particular, metagenomic experiments can help answer two key questions:

Who’s there?

In order to find out what types of bacteria are present in a sample, scientists usually sequence the DNA corresponding to a particular “marker” gene that is present in all bacteria. This is usually the 16S rRNA gene, which codes for a part of the ribosome. Marker gene profiling is a little like collecting the fingerprints of everyone who enters a building, making it possible to figure out exactly who is inside. However, it tells you nothing about what they’re doing there. What are they doing?

To get more information about what the microbes in a particular environment are doing, scientists can sequence all of the DNA present (not just a particular marker gene). This approach gives information about what kinds of genes the bacteria carry, which can give clues about their lifestyles. For example, what kinds of substances can the bacteria break down as food? Can they produce toxins that are harmful to humans?

Researchers are using metagenomics to study what kinds of bacteria are present in a wide variety of environments. One common approach is to study the microbes present in mammals’ intestines, known as the gut microbiome.

For example, researchers studying the connection between the gut microbiome and obesity sequenced the gut metagenomes of lean and obese mice. They found that the metagenomes of the obese mice contained a higher proportion of genes involved in the breakdown of dietary carbohydrates. This suggests that gut microbes in the obese mice helped them extract more energy from their food.

Did you know? Some microbes can survive temperatures as high as 140ºC, environments as acidic as pH 0 (as acidic as battery acid!), or in the complete absence of oxygen.Another approach to metagenomics is called urban microbiology, which involves studying the types of microbes present in urban environments. In one study, scientists sequenced the metagenomes of all of New York City’s subway stations. They found that almost half of the sequences belonged to organisms completely new to science, highlighting just how little we know about the microbes that surround us in our everyday life.

The data from the New York study could be used as a baseline for tracking outbreaks of infectious disease in the future. There is also a possible application to forensics: since the types of microbes present differed between subway stations, investigators might be able find out where a person had walked in recent days or weeks by sequencing the DNA on the bottom of their shoe.

Although there is still a lot to learn about the microbes that live in, on, and around us, metagenomics has opened a fascinating new window onto the microscopic world.

Learn more!

Sequencing and beyond: integrating molecular 'omics' for microbial community profiling (2015)
E. A. Franzosa et al., Nature Reviews Microbiology 13
Link to abstract. Registration of subscription required to view full text.

Scientific article discussing emerging techniques used for DNA sequencing in metagenomics.

Geospatial Resolution of Human and Bacterial Diversity with City-Scale Metagenomics (2015)
E. Afshinnekoo et al., Cell Systems (in press)

Scientific article discussing the sequencing of DNA from surfaces throughout the New York City subway system and the creation of a metagenomic map of New York.

The role of the gut microbiota in metabolic health (2015)
A. W. Janssen & S. Kersten, The FASEB Journal (in press)

An obesity-associated gut microbiome with increased capacity for energy harvest (2006)
P. J. Turnbaugh et al., Nature 444

Link to abstract. Registration of subscription required to view full text.

Scientific articles discussing the relationship between the gut microbiome and obesity.

The Uncultured Bacteria (2010)
Kim Lewis, Small Things Considered

Blog article discussing the difficulty of growing bacteria in a lab.

Stefanie Vogt

Born and raised in Edmonton, AB, I completed a Ph.D. in Microbiology & Biotechnology at the University of Alberta in 2013. Currently, I’m a postdoctoral fellow studying microbiology at the University of British Columbia. I think all areas of science are awesome, but I’m particularly interested in understanding how bacteria sense their surroundings and cause infections. Outside of the lab, I enjoy travelling, curling, and learning to play the cello.

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