Community based study offers dental disease insights

August 3, 2023

from the University of North Carolina Adams School of Dentistry

A multidisciplinary research team at the University of North Carolina at Chapel Hill, in collaboration with colleagues at the University of Pennsylvania, has published results from a community-based pediatric oral health study that found the microbiome in children's tooth biofilms plays a role in dental disease. important and previously unrecognized role.Their findings were published in the journal nature communicationsResearch shows that childhood caries, or tooth decay, is characterized by an imbalance in the oral microbiota and the interaction of certain previously unrecognized members of the bacterial community in complex ways across space and time.

Researchers, led by Kim Divaris, DDS, PhD, James Bawden Distinguished Professor, at UNC Adams School of Dentistry, spent eight years studying the complex social, behavioral and biological determinants of children's oral health. As part of this larger NIH-funded effort, the ZOE 2.0 study, researchers collected detailed clinical and biological information from 6,500 preschoolers enrolled in North Carolina's public kindergarten program, known as Head Start. Researchers collected saliva to study children's genomes, household water samples to measure fluoride concentrations, and plaque samples to assess oral microbiota, all in an effort to conduct a thorough study of oral health.

This image compares the bacteria Streptococcus mutans and Selenomonas phlegm found in the study.

This image compares the bacteria Streptococcus mutans and Selenomonas phlegm found in the study.

The paper reports the results of a very comprehensive study aimed at understanding the role of the microbiome in dental health and disease. We used data from a pilot sample of only 5% of study participants, but the investigation was conducted in the most complete manner possible ,” said Divaris, the study's principal investigator. “We started with a statewide community study, collecting detailed clinical data, social, behavioral and biological information and conducting state-of-the-art informatics and microbiome analyses.”

The UNC research team also includes Di Wu, Ph.D., associate professor of dentistry at the Adams College and associate professor of biostatistics at the UNC Gillings School of Global Public Health; Apoena De Aguiar Ribeiro, DDS, MS, PhD, associate professor at the Adams College; and Hunyong Cho, Ph.D., Postdoctoral Fellow in Biostatistics at Gillings College. They conducted clinical, bioinformatics and laboratory studies using plaque samples from more than 400 child study participants. The team collaborated with Andrea Azcarate-Peril, Ph.D., and Jeff Roach, Ph.D., of the UNC Microbiome Core Facility to perform whole-genome sequencing and RNA-sequencing analyses, then used Wu's NIH-supported custom database and state-of-the-art informatics methods. Statistics and bioinformatics project to discover new caries-related species.

“Microbiome data often have excess zeros (~70%) and high dimensionality, meaning hundreds of species and millions of genes. We evaluated 11 statistical models to address these challenges by generating comprehensive simulations “The computational pipeline we developed ensures strong candidate species, including Selenomonas sputum, for downstream validation/mechanism studies. Computational pathway analysis and correlations between species/genes can further understand disease mechanisms and support wet laboratory experimental results.

The team then attempted to replicate the findings using a second sample of children to see if the original findings held true for an independent group of peer children.

“We were able to show that the abundance of at least 16 different species is associated with dental caries, and that it's not just their presence that's important, but their presence.” “This is what they do and how they work together,” says Deva Reese said.

Further research was conducted in collaboration with a Penn State team led by co-senior author Hyun (Michel) Koo, DDS, MS, PhD, to identify the pathogenic role of these microorganisms. Koo and Penn postdoctoral researcher Zhi Ren developed a comprehensive series of biofilm studies involving computational imaging and animal experiments to validate observational, clinical and bioinformatic findings. Researchers used a novel, comprehensive multimodal discovery validation process to figure out how these oral bacteria actually cause tooth decay. They uncover an unexpected bacterial interaction and discover a new factor that causes tooth decay, Selenomonas sputum.Their findings were published on May 22 nature communications and highlighted in a recent NIH Research Matters report.

“It is clear that it will be impossible to understand how these species work together unless additional virulence assessments are employed as well as computational imaging and biogeographical studies,” Divaris said. The combination of different methods, techniques and expertise of this multidisciplinary research team was arguably key to the discovery.

“It's not just the presence of the bacteria that matters, but what they do and how they work together,” Divaris said. This unbiased, community-based study finds that species have the potential to cause dental disease in some cases not only because of their ability to produce acids and demineralize enamel, but also because of their interactions with other species in space .Investigators suggest, Selenomonas sputum As causative organisms of dental caries, this means that disrupting the relationship between these two species may provide new strategies for preventing dental disease.

As the study expands to the next phase, Divaris said they hope to analyze plaque samples already collected from the entire population of more than 6,500 study participants enrolled in the ZOE 2.0 study and to use new clinical examinations (future ZOE 3.0 research), monitor disease incidence and identify other oral health and disease biomarkers.

“Our greatest success has been the collaborative nature of this study. We had the patience to sit on data generated four years ago until we were able to establish new collaborations, bring more experts on board and allow other team members to participate and Experimental work is done to complement what we are seeing,” Divaris said. “We are grateful to our study participants, funders, and Penn collaborators. We are all pleased. This is a great example of community-based research driving biological discovery and seeing this scientific pipeline in action It was very satisfying. We saw the whole process, which is rare in dentistry. We hope to use this multimodal discovery validation process again in the near future.

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