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Biomedicine and Molecular Biology

Mapping the microbiome

Human health depends largely on the harmony of the body's cells with the trillions of microorganisms that co-exist with them. Discovering the genetic diversity of this microbial population is the goal of Human Microbiome Project, a scientific challenge that will improve the diagnosis, treatment and prevention of many diseases beyond the classic infectious illnesses

GONZALO CASINO | NOVEMBER 5, 2010

Color-enhanced electron micrograph showing the species
Salmonella typhimurium (ced cells) invading cultured
human cells

The discovery that the human body is home to a lot more microorganisms than cells has forced scientists to more closely scrutinize the microbial universe. Whether on the skin or in the body’s various cavities, there are billions of microorganisms that normally live in balance with our own cells. The proportion has found to be in favor of the microbes by 10 to 1, so if these figures are correct, our body has 90 billion microorganisms to just 10 billion human cells.

All of this microbial flora and fauna represents between 1% and 2% of a person's body weight. Placed on a scale it would be comparable to a kilo and a half of the brain, the repository of our essence and human capabilities. And even though the thousand-odd grams of microorganisms that we carry have their own genetic makeup, scientists are beginning to consider that they form a part of our identity, at least in the sense that without them it would be impossible to understand our health or the diseases we suffer. Precisely for that reason a scientific journey to explore the human microbiome has been launched.

The human microbiome can be defined as the set of the genomes of all the microorganisms (bacteria, fungi and viruses) that reside in a person. Clearly it is very difficult to sequence all of them, but you have to start somewhere. In order to obtain a reference microbiome, in December 2007 the U.S. government started a five-year and €112 million scientific program called the Human Microbiome Project (HMP), which a year later expanded to include international partners with the creation of the International Human Microbiome Consortium.

The first 178 genomes

As a result of this effort, a group of researchers connected to the HMP revealed the genetic sequence of 178 microorganisms living in or on the human body in an article published in the May 21, 2010 issue of Science. These microbial sequences are the first installment of a reference collection of almost a thousand microbial genomes (sequenced by the HMP or other international programs already underway).

The genetic data, which was gathered from public databases accessible to researchers, serves to characterize the microbial populations found in samples from healthy volunteers and patients. HMP researchers took samples of the microbial communities from five areas of the body: the digestive tract, the mouth, the skin, the nose and the vagina; it soon will expand to include two more: the male urethra and blood.

In treatment and prevention

The goal of this initiative is to better understand the scientific role of the human microbiome in our health and in diseases, specifically going beyond the classic infectious illnesses. Obesity, asthma and diabetes are among the diseases whose diagnosis, treatment and prevention may change thanks to the knowledge derived from this project. The first step is to discover the community of microbes that live in the different parts of the body, then to explore how these microbial populations have changed over time and how they relate to disease.

Mapping the human microbiome represents an opportunity to improve medicine’s approaches to numerous health problemsThe information obtained on the microbiome of the human skin has already caused some surprises. An article published in Science on May 29, 2009 showed that the diversity of microbes living on the skin was much greater than previously thought. Preliminary analysis of the microbial population of 20 areas of the skin of ten healthy volunteers identified more than 112,000 bacterial gene sequences. This information opens the way to understanding the complex genetic and environmental interactions involved in diseases such as eczema, acne or psoriasis.

Mapping the human microbiome is a major challenge but also an opportunity to improve medicine’s approaches to numerous health problems, from sexually transmitted diseases to obesity. In the current reference microbiome (the 178 sequenced genomes), researchers have identified no less than 29,693 polypeptides or bacterial proteins (a number greater than that of human genes), that were previously unknown. In the coming years researchers hope that computer analysis of the data taken from the reference microbiome and the samples of volunteers, compared with the microbial genetic data available, will help them further understand the human microbiome and associate the presence or absence of microorganisms in different diseases.
METAGENOMIC
The genetic sequencing of organisms is based on their prior culture in the laboratory. This strategy is useful for understanding the genome of the organism but limits knowledge of the diversity of the human microbiome, since many of the microbes can not grow in culture. The possibility of a genetic analysis of samples taken directly from the environment (the skin, gastrointestinal tract and other areas) has greatly expanded the focus and led to the finding that the microbiome is much larger than previously thought. This approach is called metagenomics and, together with computational analysis, has become the cornerstone for deciphering the diversity of the microbial population of human beings in health and disease.

Subjects of the article