Even with consistent brushing and flossing, some people develop more cavities than others — a difference that may be partly explained by genetics and the make-up of microbes in the mouth, according to a new study based on the largest collection of oral microbiome profiles to date.
The study, led by scientists at the Broad Institute and Mass General Brigham and published in Nature, found that human genetics has a surprisingly strong influence on the abundance of bacteria in the oral microbiome.
Researchers analyzed whole-genome sequences from saliva-derived DNA from more than 12,500 individuals and examined how interactions between human and bacterial genes relate to oral health.
“The abundance of many bacterial species in our mouths is strongly influenced by human genetics,” said senior author Po-Ru Loh, an associate member at the Broad Institute and an associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital.
“We know that the microbial environment in one person’s mouth is going to be quite different from another person’s mouth due to many factors, but genetics is a pretty strong one,” Loh added.
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Genome-to-genome interactions
To identify human–microbiota associations, the research team analyzed saliva samples that contained both human and microbial DNA. While microbial DNA in human sequencing data is often discarded, the researchers instead used it to measure the abundance of 439 common microbial species.
They identified 11 regions of the human genome associated with differences in the levels of dozens of oral bacterial species. The same genetic regions were also found to influence natural selection acting on many bacterial genes, pointing to extensive genome-to-genome interactions between humans and their oral microbiota.
“We also found that the same 11 human loci influence natural selection on dozens of different bacterial genes, so it seems like there’s a lot of interaction between human genetics and the oral microbiome,” said first author Nolan Kamitaki, a graduate student at the Broad Institute and Harvard Medical School.
One of the strongest associations involved a variant that disrupts the FUT2 gene — previously linked to gut microbiome composition — and the abundance of 58 oral bacterial species.
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Link to oral health outcomes
The researchers also used data from the UK Biobank to explore how these genetic–microbial interactions relate to oral health. A particularly strong signal involved the AMY1 gene, which encodes salivary amylase, an enzyme that breaks down starch into sugar.
The study found that variation in the number of AMY1 gene copies was associated with changes in the abundance of more than 40 oral bacterial species, many of which feed on sugars and contribute to plaque formation over time.
That same genetic variation was also linked to higher rates of denture use in biobank data, suggesting a potential connection between AMY1 copy number, oral microbial ecology and long-term tooth loss.
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Looking ahead
In addition to the biological findings, the team developed new statistical methods that allow large-scale genome-to-genome analyses to be conducted more efficiently. The researchers hope these tools will enable future studies using even larger datasets to further clarify how human genetics shapes microbial communities.
“I hope these initial results can inspire the field to get excited about what you can learn about human genetic effects on microbiomes in general — but particularly oral microbiomes, because there seem to be such strong genetic effects,” Loh said.
Related research on AMY1
Previous research has also highlighted the role of AMY1 in oral health. An early last year study from Cornell University found that the number of AMY1 copies influences how oral bacteria respond to starch, helping explain why some people are more prone to cavities and gum disease despite good oral hygiene. That work pointed to an important interplay between diet, genetics and the oral microbiota.
Related: Why some people are more prone to cavities—even with good dental habits, study finds