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Human genome encodes key factors directing our development, physiology and ability to undertake adapted responses to environmental conditions. However, our body is colonized by billions of commensal microorganisms, which are more abundant than our own body cells. These microorganisms interact with our body, and plays role in immune system maturation, digestion, nutrient production and assimilation and preventing pathogen overgrowth. These interactions play key roles in our health and well-being. In regards to their role in human physiology and health, these microorganisms are now collectively considered as an organ in our body, and therefore, their genetic content as our "second genome".
In the frame of the EU MetaHit and French Micro-Obes projects, we detailed by new sequencing technologies, the nature and the role of this still poorly characterized world. A catalogue of 3.3 millions genes has been established, largely over numbering that of human genes. The analysis of gene variability between individual by deep profiling with the Illumina or SOLiD analyzer was performed for a better understanding in the metabolic potential of human intestinal microorganisms and finding association between specific genes and phenotypes such as particular metabolic disorders.
Collectively, human can be colonized by thousands of microbial species and more variants. However, each individual displays a specific microbiota, relatively stable in the lifespan, and composed of several hundreds of species which are drawn out of this large catalog. Therefore, our "second genome" greatly varies in gene composition and abundance. In our work, the number of gene counted by deep profiling averages 540 000 by individual, but may vary between 250 000 and 1000000.
Gene association studies have been carried out by comparing gene contents of individuals included in clinical studies targeting obesity and inflammatory bowel diseases (ulcerative colitis, Crohn disease). Association could be revealed between bacterial species and diseases, raising the possibility to design genetic markers for personalized medicine and guide for the discovery of etiological factors.
Deep profiling of human intestinal microorganism genomes will provide new insight in factors affecting our health in number of pathologies. Furthermore, studies on the effect of diets, cultural practices and lifestyle affecting the composition of our "second genome" will provide guideline for preventive care and personalized medicine. |
