Researchers are looking more closely at the genome of microbial communities in the human mouth

Bacteria often have a very strong biogeography – some bacteria are abundant in specific locations, while they are absent from others – leading to major questions when applying therapeutic or probiotic microbiology: how did the bacteria get to the wrong place? How do we add the right bacteria in the right place when the biogeography came out “out of the blue”?

These questions, however, have a big hurdle, the bacteria are so small and numerous, with very diverse and complicated populations, which creates major challenges to understand which subgroups of bacteria live where and what genes or metabolic abilities allow them to thrive in these “wrong” places.

In a new study published in Genome biology researchers led by Harvard University examined the human oral microbiome and found impressive variability in bacterial subpopulations living in certain areas of the mouth.

“As microbial ecologists, we are fascinated by how bacteria can seemingly divide any habitat into different niches, but as human beings, we also have this innate curiosity about how microbes shape in our bodies,” said the author. principal Daniel R. Utter, PhD candidate in the Department of Organizational and Evolutionary Biology, Harvard University.

Recent developments in bioinformatics sequencing and approaches have provided new ways to unravel the complexity of bacterial communities. Utter and Colleen Cavanaugh, Edward C. Jeffrey Professor of Biology in the Department of Organizational and Evolutionary Biology, Harvard University, teamed up with researchers from the Marine Biological Laboratory, Woods Hole, the University of Chicago and the Forsyth Institute to apply these conditions. state-of-the-art sequencing and analysis approaches to obtain a better picture of the oral microbiome.

“The mouth is the perfect place to study microbial communities,” said co-author A. Murat Eren, an assistant professor in the Department of Medicine at the University of Chicago. “Not only is it the beginning of the gastrointestinal tract, but it is also a very special and small environment, diverse enough from a microbial point of view, so that we can really start answering interesting questions about microbiomes and their evolution.

The mouth contains a surprising amount of site-specific microbes in different areas. For example, the microbes found on the tongue are very different from the microbes found on the plaque on the teeth. “The germs of your tongue look more like those that live on someone else’s tongue than those that live on your throat or gums!” said Eren.

The team searched public databases and downloaded 100 genomes representing four species of bacteria commonly found in the mouth, Haemophilus parainfluenzae and the three oral species of the genus Roth, and used them as references to investigate their relatives sampled in the mouths of hundreds of Human Microbiome Project (HMP) volunteers.

“We used these genomes as a starting point, but we quickly moved beyond them to test the total genetic variation of the billions of bacterial cells that live in our mouths,” Utter said. “Because, at the end of the day, that’s what we’re curious about, not a few arbitrators who have been sequenced.”

Using this newly developed approach called metapangenomics, which combines pangenomas (the sum of all genes found in a set of related bacteria) with metagenomics (the study of total DNA from all bacteria in a community), allowed researchers to perform o a thorough examination of the genome of the microbes which led to a shocking discovery.

“We’ve found an extraordinary amount of variability,” Utter said. “But we were shocked by the modeling of that variability between different parts of the mouth; especially between the tongue, cheek and tooth surfaces.”

For example, in a single microbial species, researchers found distinct genetic forms that were strongly associated with a single different site in the mouth. In many cases, the team was able to identify a handful of genes that could explain the specific habitat of a particular bacterial group. Applying metapangenomics, the researchers were also able to identify specific ways in which bacteria that live freely in people’s mouths differ from their relatives grown in the laboratory.

“The resolution provided by these techniques – by directly comparing the genome of ‘domesticated’ and ‘wild’ bacteria – allows us to dissect these differences gene by gene,” notes Cavanaugh. “We were also able to identify new bacterial strains related to, but different from, the ones we have in culture.”

“After identifying some really strong bacterial candidates that could determine adaptation to a particular habitat, we would like to experimentally test these hypotheses,” Cavanaugh said. These findings could be the key to unlocking targeted probiotics, in which scientists could use what they have learned about the habitat requirements of each microbe to design beneficial microbes to land in a specified habitat.

“The mouth is so easily accessible that people have been working on bacteria in the mouth for a long time,” said co-author Jessica Mark Welch, an associate scientist at the Marine Biology Laboratory.

“Every environment we look at has these complex and complex communities of bacteria, but why is that?” said Mark Welch. “Understanding why these communities are so complex and how different bacteria interact will help us better understand how to repair a bacterial community that is harmful to our health by telling us what microbes need to be removed or added to again.” .

This study and others like it may provide new insights into the role of oral microbes in human health. “The ability to identify specific genes behind habitat adaptation has been somewhat of a ‘holy grail’ in microbial ecology,” Utter said. “We are very pleased with our contributions in this area!”