EMBL Heidelberg and Washington University scientists Peer Bork and George Weinstock respectively deciphered for the first time the genotype of gut microbiota using metagenomics data. Europeans and North American dataset respectively available from MetaHIT and HMP project were analyzed using new bioinformatics tools specially developed by Peer’s Bork group for this project.
First, next generation sequencing technology made feasible such analysis. Indeed, “Novel technologies allow for deep investigation of microbial communities in natural environments, including the gut microbiome “, says Dr Sunagawa, and “with the gains in the economics of scale in sequencing technologies and availability of metagenomic samples from a large number of individuals it was now possible for the first time to study the extent of genomic variation in gut resident microorganisms.” Dr Schloissnig explains. For the first time, “natural genomic variation of individual microbes from a large cohort of individuals down to single mutations in the most dominant gut microbial organisms.”
The most challenging part was certainly to study more than 7 Billion DNA sequences produced by randomly sequencing the collective DNA of the gut microbiota produced from 252 samples. They had to be “matched to the correct microbial species (among almost 1000) at the correct genomic region, just to get the analysis started”, says Dr Schloissnig and finally “1.56 terabases of sequence data gave rise to many computational and data-management challenges”, adds Dr Sunagawa.
The second challenge was to adapt new population genetics measures to decipher such data, “deriving some of the measures pioneered in population genetics from metagenomic data sets proved to be more difficult than we anticipated” explains Dr Sunagawa.
Using those news tools and concept, scientists found that each individual harbored a unique and stable metagenomic genotype :“Our study found, that healthy individuals retain specific strains over longer time scales, despite fluctuations in the species abundances. “ says Dr Schloissnig.
In the future, more analysis have to be performed to explore deeper the human metagenomic genotype, our second genotype and like always in such study more samples are needed. “Longer time scales and age groups will have to be included in the future to test if the finding can be generalized and to understand at which life stage, which organisms populate the human gut” said Dr Sunagawa but “one always has to balance the desire for additional samples and analysis costs.”
Finally, we asked them what will be the impact of their findings to gut clinical study :
“One can imagine performing standardized clinical screenings (ie. sequencing of a patient’s metagenome) for presence/absence of microbial genes conferring antibiotic resistance or implicated in a variety of disease states and pin-point specific mutations in them. But as already alluded before, analysis costs are still high and currently not competitive to established clinical screening procedures.” explains Dr Dr Schloissnig.
“On important aspect of this study is that the whole genome, not only specific genes, of microbial species have been profiled. To illustrate the advantage, sometimes, even a single mutation of a specific bacterium can cause pathogenisis and such mutations can now be screened for. Furthermore, combined with gene presence/absence tests, the presence of known pathogens or pathogenicity genes can be tested using the same sample, all in one go. Another important area could be monitoring the effects of antibiotic treatments or diet interventions, for example. The major limitation, however, is the current cost of this analysis. But similar to the development of computer data storage parts, it is expected that prices per unit (sequenced DNA) will continue to drop.” says Dr Sunagawa.
Without any doubt, this pioneer study provides a ultra high definition point of view of our gut microbiota.