The human microbiome is the collection of microbes that colonize the human body. The Genome Institute is applying next generation sequencing technology to analyze the genomes of these organisms and characterize the communities they form in healthy and diseased individuals. This research could ultimately provide doctors with new diagnostic and therapeutic approaches for a number of diseases.
Right now your body is teeming with microscopic organisms. In fact, they outnumber your own cells ten to one.
Thousands of different microbial species colonize our bodies and together contain over one hundred times more genes than in our genome. This group of microorganisms is called the microbiome and helps keep us alive.
"If you think of the human body – it’s made up mainly of the microbiome. Then there’s the human part of us that provides the environment for all of those microbes to live in,” says Dr. George Weinstock, Associate Director of The Genome Institute and leader of the human microbiome research that goes on here.
The Genome Institute is part of an initiative to sequence the entire genomes of 3000 individual microbes found within our human microbiome. One of the ‘Roadmap’ projects from the National Institutes of Health (NIH)'s Common Fund, this ‘Human Microbiome Project’ (HMP) has begun by sampling and sequencing the microbial communities at 18 different sites on the body – located in the mouth, nose, skin, vagina and gut. These initial samples have come from 300 young, healthy adults who are helping to provide researchers with an idea of what microbes live inside of us when we are in a normal, healthy state.
Much like the Human Genome Project was created to catalog the entire sequence of our own DNA, the Human Microbiome Project is working to catalog the genetic information of the microbes in and on the human body that contribute to our survival. By looking at the genetic variation of microbes at these different body sites, as well as among different individuals, scientists hope to understand more about how our microbiome keeps us healthy or may contribute to disease.
At the same time as they are looking at the microbiomes of healthy people, a group of Washington University researchers is working with The Genome Institute to sequence the microbiomes of certain diseased patients – including those with Crohn’s disease (an inflammatory condition affecting the gastrointestinal tract); children with fever of unknown origin; and an often fatal condition in premature babies called Necrotizing Enterocolitis, that causes inflammation of the intestinal tissue. The Genome Institute is also collaborating with researchers at other institutions who are looking at how the microbiome is associated with sexually transmitted diseases and the male adolescent urethra, as well as a project dealing with the skin microbiome as it relates to acne.
These demonstration projects were started to help guide the direction of future clinical research by looking at the potential links between the makeup of our microbiomes and specific disease states. This research could ultimately provide doctors with new diagnostic and therapeutic approaches for a number of diseases.
We often forget that microbes have been on the Earth long before we ever came on the scene. As Dr. Weinstock points out: “They’re all around us. The world is really a microbial world. They were here three billion years ago, while we arrived relatively recently. So these microbes have been on the planet for longer than any other kind of life. They have shaped the planet and are responsible for all the other life that’s here.”
Most of the microbes that we harbor do a lot for us – from helping to digest our food and absorbing nutrients we need, to churning out vitamins we can’t make ourselves and even protecting us from other harmful microbes that could make us sick. Many of these organisms are with us from birth to death and influence our growth and development. This is the impetus behind work like the Human Microbiome Project, which will help us understand more about these microscopic life forms that are so crucial to our survival.
It has taken many years and much technological advancement to get to the point where scientists can even undertake something like the Human Microbiome Project. But now, with next generation sequencing techniques, it is possible to sequence hundreds of individual microorganisms’ genomes and do it in a reasonable amount of time and at a lower cost than ever before.
But there’s a catch – unlike animals and plants, a large proportion of microbes aren’t willing to give up their DNA so readily. In fact, many of the microbes in the human body depend on other surrounding microbes and nutrients for their survival and can’t grow on their own outside of that environment.
In order to figure out what kind of microbes live in the human body, researchers are taking samples from one of five predetermined body sites (mouth, nose, skin, vagina and gut). Since they can’t sequence each microbe’s genome separately, they sequence and study the entire microbial sample at once – a field called metagenomics. The samples may contain hundreds of different microbial species, each with their own unique genome. To identify the types of species present in the sample, the scientists use key genes that are known to be associated with certain microbes. They can then look up the genomes of other microbes that have already had their entire genomes sequenced. This allows them to compare and catalog many of the important genes and species that are in a given body site sample. The more deeply they sequence each sample, the more information they can obtain about the microbial make-up of that sample.
Studying microbes within their communities rather than individually plays a key role in understanding the human microbiome. A major goal of the Human Microbiome Project is to help researchers determine the similarities and differences among the microbiome of healthy and diseased individuals. They can then characterize these communities among groups of people, and determine how they change in different health and disease states.
With the development of more advanced sequencing technologies that shorten sequencing times and reduce costs, The Genome Institute is now able to more effectively sequence the massive amounts of genetic information present in the human microbiome and discover what types of microbes are important to our health and well-being and what types we should be targeting to prevent disease. As Dr. Weinstock explains: “The microbes inside our body have a huge impact on who we are, what we do, how we feel – and we have never really defined that very precisely. That’s what we need to do to truly understand the human microbiome.”