Researchers at DTU (Technical University of Denmark) in collaboration with an international team from countries including France and China devised a method based on the co-abundance principle to easily identify the genomes (or genetic material) of unknown intestinal microorganisms. The scientists demonstrated this method on 396 human stool samples and uncovered 741 microbial species of which 181 are proposed to be completely novel. Unlike prior methods to identify bacterial species, the use of CAGs obviates the need for assembly as well the need for a database of reference genomes.
The new approach also identified 848 viruses that infect each bacterium (called bacteriophages). The balance of intestinal fauna affects human health as it is increasingly recognized disrupting such balance for example by use of antibiotics leads to disease states. Therefore modulation of the bacterial composition by viral agents is an attractive means to restore the balance. Moreover, the new insight makes possible the exploitation of viruses to attack specific bacteria, thereby adding another tool to our pharmacological arsenal which is under increasing pressure from antibiotic resistance.
The human intestine is home to many microorganisms, whose cell population is estimated to be 10 times greater than the number of human cells in an individual. Only a few species that can be cultivated in the laboratory to be sequenced by traditional methods. Identification of the different microbial species in the intestinal ecology and their interactions will lead to better understanding of relevant disease conditions such as type 2 diabetes, asthma and obesity.
In order to characterize each of the intestinal species, lead author Associate Professor Henrik Bjørn Nielsen and Professor Søren Brunak developed a new method for analyzing DNA sequences based on the co-abundance of genes. In investigating the intestine, all bacteria and viruses are sequenced together. The underlying theory is that during sequencing, the abundance of genes which are located together as a unit on a single chromosome in a sample are correlated.
According to this approach, the genomic composition of a single species is identified by grouping the genes with equal abundance as co-abundance gene groups (CAGs). The authors defined a CAG with 700 or more genes as indicative of a bacterial species (called a metagenomic species or an MGS), although smaller CAGs are still analyzed but are not promoted to the level of an MGS.
The new approach could also be applied to study the genomes of other complex microbial communities such as those in the human naso-oral tract, human skin, and in environmental settings such as soil, water reservoirs etc.
The study published in Nature Biotechnology.
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