BioEd Online

Researchers have unveiled a catalogue of genes from microbes found in the human gut. The information could reveal how 'friendly' gut bacteria interact with the body to influence nutrition and disease.

"This is the most powerful microscope that's been used so far to describe microbial communities," says George Weinstock, a geneticist at Washington University in St. Louis who was not involved in the study.

The human body contains about ten times as many microbes as human cells, and most of them live in the gut. The new study, published today in Nature¹, shows that, between them, those microbes contain 3.3 million genes, dwarfing the human genome's 23,000. The authors also find that the bacterial species in one person's gut are not as different from those of others as had been expected.

Scientists hope to use this genetic information much as they hope to use the human genome: to predict and treat disease. The goal has led to efforts around the world to sequence and characterize all the microbes in the human gut, dubbed the 'microbiome'.

Now, a group of scientists associated with a European project called MetaHIT (Metagenomics of the Human Intestinal Tract) has undertaken the biggest ever census of the bacterial genes that are present in the gut.

Mix and match

The team collected faecal samples from 124 Europeans, some healthy, others obese or overweight, and some with inflammatory bowel disease. They isolated and sequenced the DNA from the samples using high-speed sequencing techniques — a process that yields a daunting number of short DNA fragments. The team assembled the pieces into larger, continuous stretches, then compared the resulting genes to those in databases, and eliminated known human genes from the set.

On the basis of the average bacterial genome size, the authors predict that the 3.3 million genes represents about 1,000 species of bacterium. They also propose that each person's gut contains at least 160 of these species, and that about 40% of a person's gut species are shared by around half the other people in the study.

Fewer than one-third of the genes catalogued in the paper are well studied, and about 40% look like poorly studied genes from known bacteria. Finally, more than 25% of the genes have never been seen before, which suggests that unknown species may be living in our guts, says co-author Dusko Ehrlich, a microbial geneticist at the National Institute for Agricultural Research in Jouy en Josas, France.

The catalogue provides information on the genes bacteria use to process complex sugars, produce essential amino acids and vitamins, and to turn compounds foreign to the body, such as the food supplement benzoate, into useful compounds.

Elusive visitors

The authors estimate that, so far, they have sequenced about 85% of the microbial genes found in the gut. Ehrlich explains that some microbial species reside only transiently in the gut, making them difficult to catch there. Weinstock points out that species that are rare or less abundant may also be difficult to identify. And there could be greater variety around the globe: Jun Wang, a co-author on the paper and bioinformaticist at the BGI in Shenzhen, China, would like to collect data from non-Europeans to help complete the set.

The study provides some clues about how gut bacteria contribute to human health. The bacterial populations of healthy individuals are known to differ from those of people with inflammatory bowel disease, and the authors back this up, finding differences in the abundance and variety of bacteria reported for these two groups.

The work does, however, leave plenty of room to explore the effects of gut bacteria on health and disease — something, says Ehrlich, that the researchers plan to focus on in the future. Others, meanwhile, are interested in the therapeutic potential of the information. "Could these communities be used as biomarkers of the effectiveness of therapeutic intervention?" asks Jeffrey Gordon, a microbiologist at Washington University in St. Louis who was not part of the study. "Could they be the targets of therapeutic interventions? I think that is what the future holds."