The Human Microbiome Project (HMP). If asked what it is, perhaps you would see that the name resembles that of the Human Genome Project and guess that it is a large effort devoted to some sort of DNA sequencing involving humans. This is partially correct.
So what exactly is a microbiome? First, we have to wrap our heads around the astounding fact that the human body has 10 times more bacterial cells in and on it than human cells. That’s a lot of bacteria! Together, all these bacteria and other microorganisms associated with the body are called the microbiota (referring to “small life”). Second, just as a genome is the collection of all the genes of an organism, the microbiome is the collection of all the genes present in the microbiota. The HMP aims to characterize and understand the role of the human microbiome, and this summer, the culmination of years of work on the HMP has been unveiled.
Before we move on, let’s make one thing clear: bacteria have gotten a bad rap. Understandably, many people associate bacteria with disease. While pathogenic bacteria that cause disease usually get the most press, in reality, bacteria provide many benefits for both our planet and us. They are the workhorses of the world, from performing photosynthesis in the oceans, to fixing nitrogen (think of it as creating fertilizers out of thin air) to feed much of the world’s vegetation. They probably make up more of the global biomass than all other living organisms combined [1]. Not only are bacteria important on a global scale, they are also an integral part of us. Bacteria are associated with every surface of the human body, from the external skin to the internal gastrointestinal tract. Some studies even investigate the microbiome of the eye!
Humans have been studying bacteria since Antonie van Leeuwenhoek, a Dutch naturalist, invented the microscope around 1668. Using his unique talent for creating glass lenses, he was the first to observe what he termed “animalcules”, which we know now are microorganisms. van Leeuwenhoek accurately described red blood cells as well as the bacteria living in water, feces, and plaque. In essence, he was the first to describe parts of the human microbiome. At the time, his knowledge of these organisms was limited to visual observations. Now, however, scientists employ a variety of techniques to understand bacteria.
Historically, scientists study bacteria by “culturing” them: growing them on petri dishes and in test tubes to characterize their metabolism and to understand their functions. The problem with this approach is that most bacteria are very difficult to culture in a laboratory environment. Some bacteria are accustomed to very specific environments that scientists are not always able to duplicate in the lab. The advent of molecular biology, specifically the ability to sequence DNA, dramatically changed the way scientists study bacteria. By sequencing the DNA of a sample from the environment, scientists could identify some of the species present in a bacterial community, without having to culture every single species. However, in its early years, sequencing was a very labor-intensive process, and only a few sequences could be successfully recovered. Recent technology have allowed DNA sequencing to reach dizzying new speeds at dramatically lower cost, which means that scientists can finally see almost all of the species that are part of the community, not just a small subset. This advance was a major factor in initiating the Human Microbiome Project.
The Human Microbiome Project has been called “a logical extension of the Human Genome Project.”[2] Because bacterial cells outnumber human cells 10 to 1 in the body, they are thought to play an important role in human health. For example, bacteria are very important for our digestive health. Scientists now know that different kinds of bacteria are found in obese and lean people. In a study on twins published in 2008, the authors found a “core microbiota,” or a common community of bacteria, that were shared between twins, even though one was lean and the other obese [3]. However, the authors also found that there are major differences between the communities of bacteria seen in lean versus obese individuals. While this study did not provide a causative link in humans, another study used mice as a model organism [4]. By transplanting the microbiome of obese mice into lean mice, the authors demonstrated the microbiome influences the amount of fat deposition regardless of diet. This impact makes sense when you consider that most nutrients we ingest are broken down not only by human enzymes, but also by the bacteria lining our intestines.
Beyond understanding the genes present in human cells, scientists need to understand the genes and functions of the bacteria associated with us. One major goal of the HMP was to sequence samples from a range of body sites across many different people. These sites include the nasal cavity, the mouth, the skin, the gastrointestinal tract, and the genital regions (Figure 1). By comparing the communities present across a larger population, they may be able to decipher part of the variation present in humans.
Figure 1. A schematic displaying the types of samples to be analyzed as part of the HMP. (Image credit: Human Microbiome Project, NIH)
One of the studies published this summer investigated how the bacterial community in the gut has changed over time and geography[5]. By comparing hundreds of individuals from the United States, Venezuela, and Malawi, the authors found that the gut community matures over the course of the first three years of a child’s life. This ended in the “adult configuration” of the community. Additionally, samples from the U.S. were significantly different from the non-U.S. samples, indicating some microbiome variation is based on geography. Tracking the changes in the microbiota of U.S. children, they found that the “Western lifestyle” filled with processed carbohydrates influenced the type and relative proportions of bacteria in the final community. All of this information provides a foundation for future studies of the human microbiome.
Bacteria play an ever-present role in our lives. While it’s true that bacteria can cause diseases, they also help keep us healthy. With the Human Microbiome Project, scientists are finally unraveling how the complex bacterial communities in our bodies impact our health. Spurred on by new technologies, the HMP may spawn new therapies and treatments for many disorders. A recent example is the transfer of gut microbiota to treat infections of Clostridium difficile. New medicine may focus on encouraging the “good” bacteria to grow, rather than eliminating the “bad” ones.
Wesley Loo is a graduate student in the Department of Organismic and Evolutionary Biology at Harvard University.
References
[1] Whitman WB, Coleman DC, Wiebe WJ (1998) Prokaryotes: the unseen majority. Proc Natl Acad Sci USA 95:6578–6583.
[2] Turnbaugh PJ et al. (2007) The Human Microbiome Project. Nature 449:804–810.
[3] Turnbaugh PJ et al. (2008) A core gut microbiome in obese and lean twins. Nature 457:480–484.
[4] Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host and Microbe 3:213–223.
[5] Yatsunenko T et al. (2012) Human gut microbiome viewed across age and geography. Nature 486:222–227.