MetaHIT (METAgenomics of the Human Intestinal Tract) is a collaborative project, funded by the European Commission, gathering 15 institutes from 8 countries. It was born of the idea that, with the rapid development of sequencing technologies, researchers could imagine explore the genetic potential of human microbial companions and understand their impact on our health and well being. The microbes of the human intestine can reach up to ten trillion cells and represent a weight of two kilograms, exceeding that of our brain. They help us digest food, they synthesize vitamins and amino acids that are needed by our body, they protect us by educating the immune system to distinguish friends from foes. Many different diseases originate from microbial disorders. This is naturally the case of infectious diseases affecting the digestive system. But chronic diseases, which are steadily increasing in the modern societies, have also been associated with unusual changes in microbiota. Even the apparently psychological disorders such as autism may be related to an overgrowth of certain bacteria living in the intestine.
With this MetaHIT chose to focus on on two disorders of increasing importance in Europe, Inflammatory Bowel Disease (IBD) and obesity.
MetaHIT had three objectives :
- To establish an extensive reference catalog of microbial genes and genomes present in the human gut.
- To develop tools to determine which genes and genomes of the reference catalog are present in different individuals and at what frequency.
- To gather cohorts of individuals, patients and healthy volunteers, and determine which genes and genomes they carry.
- Another objective was to develop bioinformatic tools to store, organize and interpret all the information gathered, and thus establish associations between intestinal microbiota and health and disease.
The main results of the project were, so far, the establishment of a broad catalogue of microbial genes from the intestinal tract and the discovery of enterotypes. An extensive bio-informatics analysis has shown that there is a staggering number of some 3.3 million different genes among the individuals that we analyzed, 150-fold more than in our own genome! Based on this catalog, the MetaHIT consortium was able to determine the existence of enterotypes, each characterized by a dominant bacterium: bacteroides, prevotella and ruminococcus. At first glance, enterotypes do not seem to be associated with geography, food, genetic variability, age or sex of individuals. It is, therefore, a fundamental characteristic. However, the definition of enterotypes does not explain where these differences come from. They were originally defined by studying a population of 200 individuals. Today, after the study of nearly 600 people, the three enterotypes remain, but, with research ongoing, it is possible that sub-groups, or even other enterotypes, will be found. This line of investigation will allow further developments in the methodology of quantitative metagenomics.
The expected final achievements are the establishment of the methodology to characterize individual intestinal metagenomes and the discovery of associations between bacterial genes and human disease. This should pave the way for the development of novel diagnostic and prognostic tools, based on microbial genes, aiding preventive and personalized medicine. Furthermore, the detailed description of the human intestinal microbiota, its dynamics and its interaction with the human host will lead to a much more complete understanding of human biology. By combining methodological and conceptual advances our project will result in, we expect to open avenues for reasoned modulation of our microbiota. The ability to characterize individual intestinal microbiota and follow its evolution with time, coupled to the understanding of the microbe/host interactions, should allow to explore the effects of factors such as food, environment and age on the dynamics of our microbial populations, and to develop interventions to optimize these populations.
