Life Sciences Division

People are in constant contact with the bacteria found on all surfaces and in all corners of the human body, and most of these bacteria are hosted in the intestinal tract. We carry at least ten times as many bacteria as we have cells. These complex and dynamic communities have a huge influence on our physiology, our nutrition, our immune system and its development. Bacteria perform essential functions to keep us healthy. For example, they synthesize vitamins and help break down compounds that we would be unable to assimilate otherwise. They also play a major role in immune function by protecting us against pathogenic bacteria and “dialoguing” with our epithelial cells. Research has shown that there are significant differences in the metagenome of healthy people and people who are obese or have inflammatory bowel disorders, thus prompting the hypothesis that imbalances in intestinal flora could contribute to disease development.

However, unlike the human genome, the genomic content of these bacterial communities had thus far remained largely unknown. The reason for this was that as they lived without oxygen, safe in our bowels, in an environment that was difficult to characterize and reproduce, most of these bacteria could not be cultured in the lab.

Through the EU’s MetaHIT* project, which pools the resources and skills needed to analyze copious amounts of data, researchers were able to characterize the genes of bacteria found in stool samples from 124 individuals of European origin who were representative of Nordic and Mediterranean populations. To achieve this, they used a new-generation, very-high-throughput DNA sequencing method capable of analyzing all the DNA extracted from the stools, including the DNA of species that could not be grown in lab cultures. All in all, they produced and analyzed over 200 times more DNA sequencing data than any previous study on the metagenome of the human intestinal tract.

85% of the bacterial genes hosted by the human study population were sequenced, which represents 3.3 million bacterial genes: a metagenome 150 times bigger than the human genome itself. It is relatively complete, and includes the vast majority of genes previously detected in smaller studies on 13 Japanese and 18 American subjects. Out of full total of sequenced genes, 536,000 were found in each subject. Around 40% of these genes are found in at least one in two people.

A finer-grained analysis of the metagenome allowed the team to deduce that the sequenced genes came from about a thousand species of intestinal bacteria. These bacteria are usually present in humans in large proportions, although many have yet to be characterized. At least 170 of these species are hosted by every single person, while at least 75 are found in more than one in two people.

These results show that humans are relatively similar in terms of the composition of their intestinal bacterial flora. Previous studies have been unable to demonstrate this characteristic, as technical limitations only allowed them to characterize the most abundant species.

Moreover, the analysis uncovered nearly all of the 19,000 functions coded by the human intestinal metagenome. Only 6,000 of them are found in every individual, making up the minimum human intestinal metagenome needed for the intestinal ecosystem to work. They include functions needed for the synthesis of vitamins and essential amino acids, and for the breakdown of complex carbohydrates needed in our diet. Around 1,200 functions are very frequent and form the minimum genome, allowing intestinal bacteria to thrive in the intestine.

The bulk of the human intestinal metagenome has now been deciphered. The study not only describes the metagenome, but also opens the door to further research on differences in the bacterial composition of intestinal flora in healthy and sick individuals. Highlighting these differences can help drive the development of tools for early diagnosis. In the longer term, the research should platform the implementation of preventive measures and better treatments for diseases where intestinal microorganisms play a role.

----------

The European MetaHIT project

Launched in April 2008, the European MetaHIT ( METAgenomics of the Human Intestinal Tract) project coordinated by INRA Jouy-en-Josas is tasked with characterizing the bacterial genes and functions of the human intestinal flora, and studying the effects of these genes on nutrition and health. MetaHIT pools the efforts of nine top-flight European research institutes, four partners from the agrifood and pharmaceutical industries, and a Chinese research institute. It has been awarded a four-year European Commission funding grant as part of the 7th Framework Programme.

---------

[These findings were covered in a press release dated 3 March 2010.]