Archive for May, 2012

Microbiome – the extension of our genome?

Wednesday, May 30th, 2012

After the sequencing of the human genome in 2001 and updated releases that came after that, researchers thought that this breakthrough would be enough to understand humans. It was the first step for a better understanding indeed. The scientific community also believed that we would be able to understand and cure complex diseases in less than a decade. A decade is gone and we still did not. There are two major barriers that could be the causes for these under achievements: 1) we still have several questions about the human genome sequence and there are regions that we do not completely understand until today and 2) there are other layers of information contained in human organisms. These new layers include the nasal passages, oral cavities, skin, gastrointestinal tract, and the urogenital tract, coming from microorganisms that have a kind of “symbiosis” with our organism. These are the good microbes that help we digest the food we eat, help our immune system fight diseases, amongst other functions that we are just uncovering. They are named microbiota and the totality of their genomes in humans is the microbiome. More than that, a microbiome is the totality of microbes, their genetic elements (genomes), and environmental interactions in a particular environment (in this case inside our bodies). The term “microbiome” was coined by Joshua Lederberg, who argued that microorganisms inhabiting the human body should be included as part of the human genome, because of their influence on human physiology. The human body contains about 100 trillion microbial cells representing over 10 times more microbial cells than human cells, which amazes me. It is already clear that the microbiota significantly affect human physiology. For example, in healthy individuals the microbiota provide a wide range of metabolic functions that humans lack (for more details see “Microbial Ecology of the Gastrointestinal Tract”). In diseased individuals, altered microbiota are associated with diseases such as neonatal necrotizing enterocolitis, inflammatory bowel disease (IBD), and other autoimmune disorders. Thus, studying the human microbiome is an important task that has been undertaken by initiatives such as the Human Microbiome Project and MetaHIT (for details see “A human gut microbial gene catalogue established by metagenomic sequencing”). The Human Microbiome Project (HMP) is a United States National Institutes of Health (NIH) initiative with the goal of identifying and characterizing the microorganisms, which are found in association with both healthy and diseased humans (their microbial flora). Launched in 2008, it is a five-year project, best characterized as a feasibility study, and has a total budget of $115 million dollars. The ultimate goal of this and similar NIH-sponsored microbiome projects are to test if changes in the human microbiome are associated with human health or disease. This is a very important project and could be considered a second “Human Genome Project”; however with several orders of magnitude in terms of complexity. In the last century, traditional microbiology has focused on the study of individual species as isolated units. However, the vast majority of microbial species have never been successfully isolated as viable specimens for analysis, presumably because their growth is dependent upon a specific microenvironment that has not been, or cannot be, reproduced experimentally. This project is collecting samples directly from people and there is no growing in laboratories, which is important. The HMP has already shown that, interestingly, the human microbiome is different in people that are obese or have autoimmune diseases such as IBD when compared to normal controls (for more information see “Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease”). Another study has also shown that microbiomes could be continent and nation specific (see the article “Enterotypes of the human gut microbiome”). This indicates that the microbiota of these groups is different, and consequently, these differences could be important for our understanding of pathological states and also the development of new drugs against diseases. So I guess we could say that our microbiomes, which represent the genome of all microorganisms in our body, are indeed an extension of our genomes. This means that we have more complexity to deal with and more deep science will be needed to fully understand humans in the years to come! (Image Credits: Dribbble)