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Press kit item.
14/02/2006
Mapping the human intestinal metagenome
Press Kit for the International Agricultural Show – Microflora of the digestive tract
Microbes are a part of human life, living on all the surfaces and cavities of the human body. For every human cell, there are at least 10 microbial cells. What’s more, the number of genes that encode these microbial cells is thought to be some 100 times greater than that found in the human genome. These complex, dynamic microbial communities have considerable impact on human physiology, nutrition, immunity and development, and changes in them can be a major factor for many diseases. However, unlike the human genome, the genomic material of these communities, referred to as the human metagenome, is largely unknown. An international panel organised by INRA (1) in October 2005 focussed on the challenges and feasibility of an exhaustive analysis of the human metagenome.
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What exactly is metagenomics?
Metagenomics is a new and exciting field involving the analysis of genomes of all the microorganisms in an ecological niche, the majority of which cannot be grown in laboratory conditions.
To do this, the microbial population is first extracted from the niche and its DNA is purified and sequenced using high-throughput techniques. The computer analysis of a sequence enables researchers to identify major functions, such as virulence genes or genes that encode enzymes of industrial interest. Sometimes, it is even possible to reconstruct the complete genome of particularly abundant microorganisms – this in turn provides a more comprehensive view of their biological potential.
Environmental metagenomics is currently more advanced than human metagenomics. The analysis of the human oral metagenome is underway in the United States and the first analyses of the human gut metagenome have begun in Japan and the United States. However, the scale of these analyses is far from sufficient for the mapping of the complete human metagenome, given the incredible abundance and complexity of the microbial populations found in the digestive tract.
During the international meeting in Paris in October 2005, specialists in the above areas discussed the technical feasibility of sequencing the human intestinal genome, its importance for human health and industry, as well as funding options. A major consensus was found for the techniques, challenges and feasibility of the analysis of the human intestinal metagenome, which is considered a key step in the Human Metagenome Project.
A project entitled the Human Gut Metagenome Initiative was suggested, the aim of which would be to characterise the microbial communities of the digestive tract. This would enable the analysis of microbial communities based on age, nutrition, disease and the environment.
Aims and Approaches
The Human Gut Metagenome Initiative aims to establish a "reference set" for the genetic material of intestinal microorganisms. To do this, researchers will 1) sequence the complete genome of microorganisms able to be cultured (around 1,000 bacterial species); 2) develop techniques for sequencing microorganisms that cannot be cultured; and 3) classify genes of the microbial community based on metagenomic sequencing (several thousand species).
The Future of Metagenomics
Firstly, the reference set will provide an indication of the diversity of intestinal microorganisms. The discovery of new microorganisms will lead to a better understanding of gene flow and metabolic networks, the identification of new means of detoxification and the development of new bioactive products, such as peptides, enzymes and antimicrobials.
Secondly, the reference set will make it possible to develop tools for rapidly visualising microbial populations, such as DNA chips. These will in turn help researchers identify correlations between the composition and physiology of intestinal microbial communities and a person's state of health. The development of new diagnostic approaches, based on altering microbial communities that are associated with chronic disease, allergies or obesity, for instance, should one day be possible.
In addition, new prognostic approaches should also be developed that would make it possible to foresee the appearance and development of diseases and predict the response to a given medicine. A better understanding of the metabolism of medicines and xenobiotics is also an expected benefit.
Metagenomics should boost innovation and the development of new products by the pharmaceutical and food industries. New ingredients and additives are expected to appear on the markets for soluble fibres, enzymes and microbial cultures. A new, more streamlined database will be set up for functional foods, with innovative tools enabling experts to know what effect each food will have on intestinal microbial populations. This will in turn have a significant impact on the food industry in general. Finally, knowing the complete intestinal metagenome will make it possible to develop the functional genomics of microbial communities, which aims to characterise the molecular signs and various types of interaction between microorganisms and their host. Thus, the role of microorganisms in the development and maturation of the immune system and also in immunosenescence should be better understood in the future. Insight into the role of intestinal microorganisms used as vaccine adjuvants should allow for the optimisation of live vaccines and the development of new immunisation strategies.
International Consortium
To achieve the ambitious goals of the Human Gut Metagenome Initiative, a large International Consortium is being created with laboratories and other relevant institutions. This will allow for sharing of the resources and expertise needed for such a complex, large-scale effort, which goes beyond that of the sequencing of the Human Genome. The division of labour, synergies and scale economies resulting from this international initiative will help reduce costs and increase the rate at which new discoveries are made. The creation of the Consortium will make it possible to standardise procedures and carry out quality control of data, to coordinate different analyses, to circulate data and share resources amongst the scientific community as well as to keep the reference set, the genetic library of intestinal microorganisms, up to date. A particularly important responsibility of the Consortium will involve promoting the funding of the Human Gut Metagenome Initiative at an international level. The Consortium should be operational at the end of the first quarter of 2006.
* Steering Committee: S. Dusko Ehrlich, INRA Microbial Genetics Unit, Jouy en Josas; Joël Doré, INRA Unit for Ecology and Physiology of the Digestive Tract, Jouy en Josas; Xavier Leverve, Scientific Directorate for Human Nutrition and Food Safety, INRA Paris; Pierre Monsan, CNRS/INRA/INSA Joint Research Unit for Biotechnologies and Bioprocesses, Toulouse; Jean Weissenbach, Genoscope-Centre National de Séquençage, Evry.
(1) The international panel was made up of 75 participants from Asia (China, Japan), the Americas (Brazil, Canada, United States) and Europe (Germany, UK, Belgium, France, Ireland, Netherlands, Switzerland), including scientists, physicians, manufacturers and administrators of research institutions (ANR, DGR at the European Commission, NSF and NIH).
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Written by :
INRA press service, phone: +33 (0)1 42 75 91 69
Contacts :
S. Dusko EHRLICH
Tel: 01 34 65 25 10 - Dusko.Ehrlich@jouy.inra.fr
Microbial Genetics Research Unit, Department of Microbiology and the Food Chain,
INRA Centre of Jouy-en-Josas
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