The Human Microbiome Project (HMP) is an extensive scientific initiative conducted in the US with the goal of identifying and characterizing the highly diverse microscopic organisms that dwell at different sites in the human body. Using state-of-the-art DNA sequencing technologies, scientists are trying to define biological links between the trillions of microbial "residents" and various physiological conditions, including diseases.
"I'm only flesh and blood", all of us occasionally claim. But is that really the case? Studies performed in the last few decades revealed that we humans are far from being the isolated, well defined beings we believe ourselves to be. On the contrary: in fact, we serve as a habitat for trillions of microbes with which we have a symbiotic relationship, and without which we couldn't exist!
Bacteria-rich regions in the human body. Image adopted from the HMP.
In a series of fascinating studies performed under the umbrella of the Human Microbiome Project (funded by the US National Institutes of Health, NIH), scientists are working day and night to thoroughly characterize the whole ensemble of viruses, bacteria and eukaryotes (yeast, fungi, etc.) that reside within different regions of the human body. The main objectives of the HMP as specified by the NIH are:
1. Sequencing the genome of the microorganisms that reside in the human body and preliminary characterization of the human microbiome.
2. Exploring any relationships between changes to the microbiome and various human diseases.
3. Developing computational methods for dealing with the vast amounts of data associated with such a large-scale project.
4. Establishing a center for coordinating and analyzing the data obtained from the project.
5. Establishing a resource repository.
6.Studying the ethical, legal and social implications of the project.
As part of this project, scientists are taking a census of the microbial communities that reside in various sites of the human body, including the nasal and oral cavities, the skin, the digestive tract, the urinary tract and the male and female reproductive systems. You may have heard some of the names of the roughly 10,000 (!) different microorganism species that inhabit the human body. Examples include Escherichia coli bacteria that reside in our colon, the various Candida yeast species that are the culprits in many genital infections and the Helicobacter pylori bacteria that form ulcers in the stomach wall (and probably also affect our appetite). These species include pathogenic (i.e. disease causing) microbes that flourish when the immune system is weakened, neutral species that are not known to interact with the host and species that actually benefit the human host such as Lactobacillus acidophilus (the probiotic bacteria added to yogurt) that is important for the normal development of the immune system in infants.
Importantly, the body sites that are being inspected in these studiesare those that are continuously exposed to the external environment and have thus evolved to accommodate different microorganisms. One must remember that other sites in the human body (the blood, the brain and others) must be "off limits" for microbes, otherwise severe illness and even death may ensue.
The distribution of several bacterial species at different sites in the human body. Image adopted from the HMP.
Preliminary results have revealed, for example, that there is no correlation between the diversity of microorganism populations in different body sites (termed "alpha diversity")and the diversity between individuals ("beta diversity"). For instance, even though our saliva contains a wide variety of microorganisms (high alpha diversity), the saliva of most people contains quite similar communities of microorganisms (low beta diversity). In contrast, while the alpha diversity of skin microorganisms (the variety of microbes on the skin) is moderate in comparison to other body sites, the beta diversity of the skin is very high (meaning that different people carry different microorganisms on their skin).
Another interesting finding was that while people differ in the microorganisms that they carry, a surprising similarity was found with respect to metabolic parameters that characterize these microbial communities, including breakdown of sugars and processing of amino acids. In other words, different microbial communities that are present in the intestines of different people exhibit similar metabolic traits. This similarity is probably a result of the fact that each of the body sites investigated provides a distinct growth environment for microbes, including varying levels of oxygen, moisture, acidity, etc. These conditions dictate to the microbial "guests" the metabolic pathways that would best support their survival. Importantly, this uniformity in the metabolic state is often lost in disease, and vice versa, its loss can lead to disease. A well known example for this is the correlation between antibiotic consumption and obesity and autoimmune diseases. Antibiotics eliminate a wide range of gut bacteria in a non-specific manner and can thus impair the normal development of the immune system in infants.
Studies that focused on particular sites in the body gave rise to more interesting findings and pointed to more correlations between perturbations to the microbiotic populations and physiological changes (pregnancy, disease). For example, a difference was found between the virome (the genomes of all viruses) in the blood of babies with fever of unknown origin compared to the blood virome in healthy babies. This indicated that the fever in these babies is likely a result of a viral infection in the blood. As simple and easily attainable means for diagnosing the causative agent are scarce, many physicians prescribe antibiotics to babies with fever as a preventive measure in order to combat a potential bacterial infection (antibiotics do not kill viruses). Development of methods for detecting viruses that cause fever in babies can cut down the number of antibiotics prescriptions and thus reduce the emergence of bacterial resistance to antibiotics.
The human microbiome is an inseparable and vital component of the human body, as much as the body organs themselves. Throughout history scientists studied the organs of the human body in great detail in order to gain insight into how they work and what can be done when things go wrong. Nowadays, modern scientific techniques allow us to inspect this additional, clandestine “organ” that is not composed of human cells but rather a fabulous diversity of microscopic creatures.
Image adopted from the HMP.
Further information can be obtained in the following links:
The Human Microbiome Project on the NIH website.
An interactive slideshow on the Scientific American website.