Project

Metagenomics of the Human Intestinal Tract

A detailed understanding of human biology will require not only knowledge of the human genome but also of the human microbial metagenome. Humans live in constant association with microbes that are present on surfaces and in cavities of the human body, and even within our cells. The number of our microbial companions exceeds by at least ten-fold those of cells of our own body and the number of unique genes they encode is predicted to be at least 100-fold greater than the number of genes in our own genome. This complex and dynamic microbiota has a profound influence on human physiology, nutrition, and immunity. Disruptions in these human-associated microbial communities are a significant factor in many diseases. The ensemble of the genomes of human-associated microorganisms represents the human metagenome. Understanding the dynamic and variable nature of human microbial communities is a critical aspect of the challenge before us. Defining this dynamic diversity represents the next frontier of genomics. To progress towards this ambitious goal we focus on the microbiota of the intestinal tract, which plays a particularly important role in human health and well-being.

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Microbes in our intestine

The microbiota of the human intestine is composed of a very high number of microbial cells which reach up to ten trillion within a few days after birth and can represent a weight of two kilograms. The intestinal microbes not only help digest food and synthesize vitamins that are needed by our body, they also protect us, by educating the immune system to distinguish friends from foes, and controlling production of various drug-like metabolites. Many different diseases originate from microbial disorders. This is naturally the case of infectious diseases affecting the digestive system. But non-infectious diseases such as obesity have also been associated with unusual changes in microbiota. Even apparently psychological disorders such as autism may be related to an overgrowth of neurotoxin-producing bacteria living in the intestine.

Expected achievements and their impact

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 unprecedented description of the human intestinal microbiota, its dynamics and its interaction with the human host that we aim to provide will lead to a much more complete understanding of global human biology.

Last but not least, 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. This should open novel possibilities to improve human health and well-being.