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Dr Christina Adler’s work into the oral microbiome may reveal how genetic and environmental factors influence their development and drive disease such as tooth decay in children. Chloe Warren reports
Dr Christina Adler began her love of dentistry a little earlier than most: about 10,000 years earlier to be precise. After learning about the significance of teeth in the context of forensic science as part of her undergraduate degree, she was inspired to consider what else a detailed analysis of our teeth might reveal.
“People studying ancient anthropology used to just chip the calculus off the teeth they were examining and get rid of it,” she laughs. “They didn’t see it as a useful thing. But we now know that it preserves DNA really well.” That DNA includes not just human DNA, but that of the oral microbiome. Dr Adler subsequently spent part of her PhD at the Sanger Institute in Cambridge, refining genetic extraction and analysis methods to look more closely at the ancient human microbiome.
Dr Adler made a sizable impact in her field. Her findings were published in Nature Genetics, marking the beginning of an entirely new branch of research—paleo microbiology— where the ancient microbiome is dissected to shed light on diets and health throughout human history.
“Before agriculture and industrialisation, there was hardly any decay or periodontal disease—we had great teeth!” she says. “While there is some evidence of plaque removal in certain ancient cultures, generally people didn’t brush their teeth—if you have a balanced oral microbiome, then you don’t need to.”
Learning from the past
Fascinated though she was by the work, it struck her as ironic that her research was telling her more about ancient oral microbiome than was known at the time about its modern counterpart. Although the concept of an oral microbiome is far from new, its significance and complexities are only just being discovered. “There had been some attempts to disrupt the oral microbiome in favour of a ‘healthy’ one before, but they were single species type approaches,” explains Dr Adler.
Her ‘omics’ methods instead encompass all the bacterial species, so she can take a global view of the oral bacterial populations. “But we don’t know how early these species need to be there to predispose you to good oral health, or what kind of things make a difference to those species over time.”
Curious about where her insights might take her in the field of public health, she moved to the University of Sydney following her PhD in Adelaide, and took up a teaching and research position at the School of Dentistry.
“Because I started out looking at paleo microbiology, I was really interested in evolution and how things change over time, and that’s really informed how I look at the modern microbiology research; it’s different to how a more traditional microbiologist may come at it.”
It wasn’t only Dr Adler who saw the value, clinically, in her perspective. An old colleague of hers from the University of Adelaide was Professor Grant Townsend, well known in research circles for his pioneering work on twin cohorts. The professor passed away in 2019, but shortly after Dr Adler moved to Sydney, he sought her professional expertise. “He told me, ‘Look, I can really see the synergy between what you’re doing and what we’re doing,’ and I just thought, ‘This is amazing, because with this cohort I can actually test out some of my ideas about diet and inheritance and environment—all the ideas I had during my PhD.’”
While Dr Adler was accustomed to dealing with the scant evidence of an anthropological dig site, this new project offered its own opportunities and challenges.
“I tend to work on the biofilm—the plaque—the most. That’s quite comparable to calculus, but of course kids don’t tend to get calculus. You could also use saliva, but that contains a lot of host DNA, so human DNA. Saliva tends to be 90 per cent you and 10 per cent bugs, whereas the biofilm is 10 per cent you and 90 per cent bugs.”
Along with her plaque and saliva samples, she is now working with chemists who have the cohorts’ baby teeth at their disposal (and thus environmental and dietary information right from the third trimester), and epidemiologists armed with medical histories and anthropometrics, as well as patient survey data. The cohort is now managed by Dr Toby Hughes, whose primary focus is on craniofacial growth and development.
Unlike the gut microbiome, the oral microbiome tends to be far more stable in its nature. This raises some interesting opportunities for early intervention, as well as for maternal health.
“We inherit our bacteria from our parents, so the microbiome starts to develop from conception. The oral microbiome increases in its diversity as we age, then declines again in old age, so we do have this pattern. It’s interesting to consider though—how many generations will it take for us to repair an unhealthy microbiome, and even if we do manage to modify it, will it be passed down?”
As well as the link between oral microbiome and oral and general health, Dr Adler is particularly interested in the relationship between the oral microbiome and dental caries.
“It’s one of the most common chronic conditions worldwide, and in Australia it’s not getting any better. It did go down—it was even higher before we added fluoride to the water—but since the 80s, it’s been climbing again. The other really sad thing is that it’s the most common reason kids are admitted for general anaesthetic in Australia for non-urgent matters.”
In collecting longitudinal samples and data from monozygotic and dizygotic twins throughout their development, the research team can look for links between the oral microbiome and dental health, and how much of that is due to genetics and how much is due to environment: nature vs nurture. “For example, could we see what’s happening in a six-month-old and use that to predict what might happen by the time they’re eight? How similar are certain bacterial species in twins—is there a big influence of parental genetics? What is the role of diet? Broadly, we’re trying to figure out what is the role of the microbiome in dental decay.”
The future of therapy
Dr Adler knows as well as any dentist that the best way to reduce dental cavities is to improve oral hygiene behaviour, but she also knows that despite the public health campaigns, and the hard work of dental health professionals, instilling behavioural change is incredibly challenging.
“While preventative measures are effective, there will always be a portion of people for whom a therapeutic option could be the only option. There’s already been a very strong cultural shift towards preference for minimally invasive procedures amongst dentists, so really this is following that same line in treatment planning: away from mechanical approaches and towards biological approaches.”
In identifying how the oral microbiome is determined, and which combinations of bacterial species make for a ‘good’ microbiome, preventative—and even —curative therapeutics could be developed and introduced in a holistic manner along with oral hygiene practice. “There is big potential there; could we recommend probiotics or prebiotics, or could we even build therapeutics on a microbiome scale?”
While she is hesitant to speculate on what the findings of her teams’ studies may be—they still have many years of sampling and analysis ahead of them—Dr Adler sees the research as a continuation of dental health tradition, wherein beneath all preventative and curative measures is a solid evidence base. “Most of us know about microbiomes in general, and dentists have heard of oral microbiomes, but we’re really at the beginning stages of understanding what it all means clinically—how might we modify and manipulate these systems to benefit health?”