We all have E. coli bacteria in our gut but each of us carries a version that is genetically slightly different. The same can be said of most gut microbes: our own gut metagenome, that is the sum of all the genomes of all our gut microbes, appears to be really specific to each of us, and to remain stable over time. For the first time, researchers from the European Molecular Biology Laboratory (EMBL) have studied this metagenome at such a high resolution that individual mutations in the various strains could be analyzed.
Their findings, published in Nature, could have widespread consequences in medicine: gut microbes are known to be essential for functions as vital as digesting food or providing vitamins, but can also be involved in diseases if they carry certain mutations.
The scientists analysed the gut metagenome of 207 individuals from Europe and the U.S., matching more than 7 billion pieces of DNA (of 100 lettres each) to the genomes of our most abundant gut microbial species.
“This large-scale analysis showed that, at least when healthy, we carry a unique set of bacterial strains and their mutations in our gut, over a long time,” explains Peer Bork who led the study at EMBL. “It is like a second genetic signature, but one that probably does not come from our parents but that we acquire from the environment in early childhood.”
When comparing the specific mutations from the same individual over time, the researchers found that the metagenome remains stable for at least one year, and probably much longer when the individuals are healthy. Results also show that there is only little geographic difference when comparing metagenomes of European with North-American individuals. This indicates that gradual adaptation is possible.
For each individual, approximately 6 billion DNA letters of their gut metagenome have been analysed, many more than the 3.3 billion DNA letters of human DNA that we inherit from each of our parents. These 6 billion DNA letters belong to hundreds of microbes, each with thousands of different strains or variants: mapping each DNA fragment of the metagenome to its right place, in the right bacterial genome, is extremely complex. To achieve this breakthrough and carry the analysis down to the single DNA letter, scientists had to develop various new computational methods. In the current study more than 10 million mutations have been detected in the 207 individuals.
All these detailed data is now stored in public databases, such as dbSNP, freely available to the scientific community. These findings could lead to the development of new approaches in the identification of gut diseases, pathogens or antibiotic resistance. On the longer term, they may also open new avenues for personalized therapies.