A closer look at the genomes of microbial communities in the human mouth

The incredible, variable bacteria living in your mouth.

Micrograph of Rothia Cells
Micrograph showing Rothia cells (light blue) in their native habitat, a bacterial biofilm scraped from the human tongue. CREDIT Photo credit: Jessica Mark Welch, Marine Biological Laboratory.

Some bacteria are abundant in specific locations while absent from others. But, how did the bacteria get into the wrong place? How do we add the good bacteria into the right place when the biogeography has gotten ‘out of whack’?

Bacterias are so tiny and small that it is difficult to characterize which subgroups of bacteria live and what genes or metabolic abilities allow them to thrive in these ‘wrong’ places.

Scientists from Harvard University studied the human oral microbiome and discovered impressive variability in bacterial subpopulations living in some mouth regions.

Co-author A. Murat Eren, assistant professor in the Department of Medicine at the University of Chicago, said, “The mouth is the perfect place to study microbial communities. Not only is it the beginning of the GI tract, but it’s also a very unique and small environment that’s microbially diverse enough that we can start to answer interesting questions about microbiomes and their evolution.”

“The mouth contains a surprising amount of site-specific microbes in different areas. For instance, the microbes found on the tongue are very different from the microbes found on the teeth’ plaque. Your tongue microbes are more similar to those living on someone else’s tongue than they are to those living in your throat or on your gums!”

Scientists scoured through public databases and downloaded 100 genomes that represented four bacteria species commonly found in the mouth, Haemophilus parainfluenzae, and the three oral species of the genus Rothia. Using these bacterias as references, scientists tend to discover their relatives sampled in hundreds of volunteers’ mouths from the Human Microbiome Project (HMP).

Lead author Daniel R. Utter said, “We used these genomes as a starting point, but quickly moved beyond them to probe the total genetic variation among the trillions of bacterial cells living in our mouths. Because that’s what we’re curious about, not the arbitrary few that have been sequenced.”

Using the approach called metagenomics, scientists deeply examined the genomes of the microbes, which led to a shocking discovery. They found a tremendous amount of variability. What was more surprising was the patterning of that variability across the different parts of the mouth, specifically, between the tongue, cheek, and tooth surfaces.

For example, within a single microbe species, the researchers found distinct genetic forms strongly associated with a single, different site within the mouth. In many cases, the team was able to identify a handful of genes that might explain a particular bacterial group’s specific habitat. Applying metagenomics, the scientists were also able to identify specific ways free-living bacteria in people’s mouths differed from their lab-grown relatives.

Colleen Cavanaugh from the Department of Organismic and Evolutionary Biology, Harvard University, said, “Having identified some strong bacterial candidates that could determine adaptation to a particular habitat, we would like to test these hypotheses experimentally. These findings could potentially be the key to unlocking targeted probiotics, where scientists could use what’s been learned about each microbe’s habitat’s requirements to engineering beneficial microbes to land in a specified habitat.”

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

“Every environment we look at has these complicated, complex communities of bacteria, but why is that? Understanding why these communities are so complex and how the different bacteria interact will help us better understand how to fix a bacterial community that’s damaging our health, telling us which microbes need to be removed or added back in.”

Utter said“This study and others like it can provide new insights on 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. We are very excited about our contributions in this area!”

Journal Reference:
  1. Daniel R. Utter, Gary G. Borisy, A. Murat Eren, Colleen M. Cavanaugh, Jessica L. Mark Welch. 2020. Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity. Genome Biology. DOI: 10.1186/s13059-020-02200-2