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Different genetic fingerprint
ST. LOUIS—The massive collection of microbial DNA in the human intestine is just as individualized and varied as DNA, according to a study by researchers at Washington University School of Medicine in St. Louis and the European Molecular Biology Laboratory in Heidelberg, Germany.
The researchers hope the analysis of the microbial DNA will shed some light on the selective forces that shape the intestine's microbiome—the collection of microbes and their genes.
Published online Dec. 5 in Nature, the study, which is the first to catalog genetic variation of microbes that live in the gut, shows the heterogeneity of the microbes that extract nutrients from food, synthesize vitamins, protect against infections and produce compounds that naturally reduce inflammation. The genomic variations can help scientists to understand how microbial genes work together with human genes to keep people healthy or cause disease.
"Individuals have unique metagenomic genotypes, which may be exploitable for personalized diet or drug intake," explains Dr. George Weinstock, associate director of the Genome Institute at Washington University, who says that human beings can "be identified by the collective DNA of our gut microbes." Conversely, the microbe Enterococcus faecalis can cause life-threatening infections, particularly in a hospital setting, because it often is resistant to antibiotic treatments.
The study is the result of two big projects done in parallel, adds Weinstock. Neither of those studies, which were designed to catalog the diverse species of microbes that live in and on the body—the Human Microbiome Project, funded by the National Institutes of Health, and the Metagenomics of the Human Intestinal Tract (MetaHIT) project, funded by the European Commission—looked at the genetic variation of the microbial genomes in the body.
Weinstock and his colleagues analyzed the microbial DNA in 252 stool samples from 207 individuals living in the United States and Europe who had participated in the previous studies. They focused on 101 species of microbes commonly found in the intestine, identifying more than 10 million single-letter changes in the collective DNA of those microbes, as well as many other DNA alterations, including insertions, deletions and structural changes to see which variants could have an impact on the host. The study involved a trillion nucleotides of data and the need for the researchers to develop their own software.
"Some bacterial genes have more variants than others, especially those that transfer materials between bacteria," Weinstock says. "The interaction between bacteria and host cells is precise. It can't be functional if it has too many variants."
What surprised Weinstock and his colleagues was that the "microbial DNA in the intestine is remarkably stable, like a fingerprint." Even after a year, the researchers could distinguish individuals by the genetic signature of their microbial DNA.
"While we don't know how microbes shape our lives or what their implications are for diseases, some variants make bacteria more damaging or may not provide a useful function," Weinstock says. "In the intestine, research has suggested that an imbalance of bacteria may contribute to irritable bowel syndrome, Crohn's disease and even obesity. There could be a drug treatment that could modify the structure of the microbiome and make for more or less inflammation."
Now Weinstock and his colleagues plan to look at the bacterial genes in detail as one of their next projects. The Human Microbiome Project looked at other sites besides the intestines, and now Weinstock's team is looking at the same species of bacteria on different sites of the body to see whether they behave the same way.
The researchers are asking new questions: When something is introduced in the intestines, does it stay or can it be replaced? If bacteria had deleterious variants, what would be the impact of replacements?
"Because there is such a large number of variants, the spectrum of variants is unique in each person," Weinstock says. "Bacteria now have a signature."
Because of that signature, Weinstock expects to look at bacteria population genetics in lots of different people, with each subject being a "geographic region" that changes or stays the same based on the properties of the organisms living in it.
"Then we can see how different diets, ages, genders and other factors can influence the variants," he concludes.