ST. LOUIS—The massive collection of microbial DNA in thehuman intestine is just as individualized and varied as DNA, according to astudy by researchers at Washington University School of Medicine in St. Louisand the European Molecular Biology Laboratory in Heidelberg, Germany.
The researchers hope the analysis of the microbial DNA willshed some light on the selective forces that shape the intestine'smicrobiome—the collection of microbes and their genes.
Published online Dec. 5 in Nature, the study, which is the first to catalog geneticvariation of microbes that live in the gut, shows the heterogeneity of themicrobes that extract nutrients from food, synthesize vitamins, protect againstinfections and produce compounds that naturally reduce inflammation. Thegenomic variations can help scientists to understand how microbial genes worktogether with human genes to keep people healthy or cause disease.
"Individuals have unique metagenomic genotypes, which may beexploitable for personalized diet or drug intake," explains Dr. GeorgeWeinstock, associate director of the Genome Institute at Washington University,who says that human beings can "be identified by the collective DNA of our gutmicrobes." Conversely, the microbe Enterococcus faecalis can cause life-threatening infections, particularlyin a hospital setting, because it often is resistant to antibiotic treatments.
The study is the result of two big projects done inparallel, adds Weinstock. Neither of those studies, which were designed tocatalog the diverse species of microbes that live in and on the body—the HumanMicrobiome Project, funded by the National Institutes of Health, and theMetagenomics of the Human Intestinal Tract (MetaHIT) project, funded by theEuropean Commission—looked at the genetic variation of the microbial genomes inthe body.
Weinstock and his colleagues analyzed the microbial DNA in252 stool samples from 207 individuals living in the United States and Europewho had participated in the previous studies. They focused on 101 species ofmicrobes commonly found in the intestine, identifying more than 10 millionsingle-letter changes in the collective DNA of those microbes, as well as manyother DNA alterations, including insertions, deletions and structural changesto see which variants could have an impact on the host. The study involved atrillion nucleotides of data and the need for the researchers to develop theirown 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 befunctional 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." Evenafter a year, the researchers could distinguish individuals by the geneticsignature of their microbial DNA.
"While we don't know how microbes shape our lives or whattheir implications are for diseases, some variants make bacteria more damagingor may not provide a useful function," Weinstock says. "In the intestine, researchhas suggested that an imbalance of bacteria may contribute to irritable bowelsyndrome, Crohn's disease and even obesity. There could be a drug treatmentthat could modify the structure of the microbiome and make for more or lessinflammation."
Now Weinstock and his colleagues plan to look at thebacterial genes in detail as one of their next projects. The Human MicrobiomeProject looked at other sites besides the intestines, and now Weinstock's teamis looking at the same species of bacteria on different sites of the body tosee whether they behave the same way.
The researchers are asking new questions: When something isintroduced in the intestines, does it stay or can it be replaced? If bacteriahad deleterious variants, what would be the impact of replacements?
"Because there is such a large number of variants, thespectrum of variants is unique in each person," Weinstock says. "Bacteria nowhave a signature."
Because of that signature, Weinstock expects to look atbacteria population genetics in lots of different people, with each subjectbeing a "geographic region" that changes or stays the same based on theproperties of the organisms living in it.
"Then we can see how different diets, ages, genders andother factors can influence the variants," he concludes.