Scientists, for the first time, have mapped the genetic diversity of microbes residing in the human gut and mouth. They found 46 million genes, with at least half of these genes appearing to be unique to each individual—a diversity far exceeding the researchers’ expectations.
The study, which was published 12 August 2019 in the journal Cell Host & Microbe as “The Landscape of Genetic Content in the Gut and Oral Human Microbiome,” is the first to include DNA samples from bacteria that reside both in the mouth and the gut; previous studies have focused on one or the other. The authors, from the labs of Aleksandar Kostic and Chirag Patel at Harvard Medical School (HMS), say their work is just the beginning of efforts to analyze the entire genome collective of the human microbiome.
“The field still does not have a grasp on the scope of the microbiome’s genetic content—in the gut and otherwise—a question crucial for understanding microbial function in the context of host disease,” they wrote.
Earlier work found that changes in both bacterial count and bacterial content have been linked to the development of conditions ranging from cavities in teeth and gut infections to more serious ones, including chronic inflammatory bowel disease (IBD), diabetes, and multiple sclerosis.
“Ours is a gateway study, the first step on a what will likely be a long journey toward understanding how differences in gene content drive microbial behavior and modify disease risk,” said first author Braden Tierney, an HMS graduate student, in a press release.
Scientists estimate that the human microbiome—the collective body of microbes that populate our guts, mouths, skin, and other parts of the body—contains trillions of bacteria, most of them harmless, many beneficial, and some disease-causing.
Cataloging the array of microbial genes could inform the design of precision-targeted treatments, said Kostic, assistant professor of microbiology and an investigator at the Joslin Diabetes Center. “Such narrowly targeted therapies would be based on the unique microbial genetic make-up of a person, rather than on bacterial type alone.”
Additionally, profiling the unique genes that make up a person’s microbiome could act as a form of microbial fingerprinting that provides valuable clues about past exposures to different pathogens or environmental influences, as well as disease predispositions, Kostic added.
In the study, the HMS researchers set out to estimate the number of microbial genes in the human body, gathering all publicly available DNA sequencing data on human oral and gut microbiomes. In total, they analyzed the DNA of some 3,500 human microbiome samples, of which more than 1,400 were obtained from people’s mouths and 2,100 from people’s guts.
They found nearly 46 million bacterial genes in the 3,500 samples—about 24 million in the oral microbiome and 22 million in the gut microbiome, the researchers found. Based on their findings, the researchers concluded that we may never know the actual number of genes present in the collective human microbiome.
But what they did discover may be more relevant to future clinical applications. More than half of all the bacterial genes (23 million) occurred only once, rendering them unique to the individual. The researchers termed these unique genes “singletons.” Of the 23 million singletons, 11.8 million came from oral samples and 12.6 million came from intestinal samples.
Researchers noted that these singleton genes also performed different functions than other genes. The analysis showed that commonly shared genes appeared to be involved in functions critical to a microbe’s day-to-day survival, such the consumption and breakdown of enzymes, energy conversion, and metabolism. The singletons tended to carry out more specialized functions, such as gaining resistance against antibiotics and other pressures and helping to build a microbe’s protective cell wall, which shields it from external assaults.
This finding, the team said, suggests that singleton genes are key parts of a microbe’s evolutionary survival kit.
“Some of these unique genes appear to be important in solving evolutionary challenges,” Tierney said in the release. He and his colleagues hypothesize that bacteria’s ability to evolve their DNA rapidly in response to changes in the host environment could drive the genetic diversity they observed.
“If a microbe needs to become resistant to an antibiotic because of exposure to drugs or suddenly faces a new selective pressure, the singleton genes may be the wellspring of genetic diversity the microbe can pull from to adapt.”