Dentistry faculty member part of collaborative grant researching how to improve fluoride’s efficacy in preventing childhood caries4 min read

Ann Arbor, Mich., March 27, 2025 – A School of Dentistry faculty member is one of three principal investigators who have received a five-year, $5.2 million federal grant to research how to enhance the efficacy of fluoride in preventing childhood caries.

The grant, from the National Institute of Dental and Craniofacial Research (NIDCR), will explore how certain microbes in the mouth resist fluoride and thus reduce its effectiveness in preventing caries. The study is important because it is estimated that half a billion children around the world have untreated caries, leading to pain, impaired nutrition, reduction in school productivity, and significant costs for care.

The RM1 Collaborative Program Grant requires the participation of researchers from different disciplines with complementary expertise in order to achieve what the grant language calls “disruptive innovations” in dental, oral and craniofacial research. The three Principal Investigators at the University of Michigan leading the project are:

• Livia Tenuta, an Associate Professor in the Department of Cariology, Restorative Sciences and Endodontics at the dental school.

• Randy Stockbridge, an Associate Professor in the Department of Molecular, Cellular and Developmental Biology in the College of Literature, Science and the Arts (LSA).

• Luis Zaman, an Assistant Professor in the Department of Ecology and Evolutionary Biology in LSA with expertise in computer science and complex systems.

Fluoride used from different sources, like fluoridated water, fluoride toothpaste and mouthwashes, significantly reduces the development of caries, but microbes in the mouth are able to resist fluoride. Certain microbes, like the bacterium Streptococcus mutans and the fungi Candida albicans, contribute to the biofilm on teeth that causes caries, enhanced by sugars ubiquitous in modern diets. These microbes have cell membrane proteins that expel fluoride that enters their cells, reducing the fluoride’s antimicrobial effect against them, and leading to a harmful biofilm.

In this project, a team of specialists in structural biology, cariology, and modeling and prediction of microbial systems will develop a new class of anticaries therapy. The goal is to identify fluoride export inhibitors for the caries-causing microorganisms, determine their mechanism of action and learn their effects on the complex dental biofilms. By developing new and effective fluoride efflux inhibitors, researchers hope to increase the anticaries effect of fluoride in over-the-counter products like toothpastes and mouth rinses to combat early childhood caries.

“Microbes have different types of proteins that protect them against fluoride,” Tenuta said. “We want to target the specific proteins associated with the microbes that causes caries. If we can inhibit them, then fluoride will be more toxic for these specific microbes.”

The study will also establish methods to predict the effect of different treatments according to the patient’s specific oral dysbiosis, so that personalized treatment regimens can be used to maximize anticaries effects.

Tenuta called the new grant a “team science” approach that benefits from the contributions of researchers across a variety of specialties. In addition to the research done in the labs of the three Principal Investigators, three other participating investigators are included in the grant – U-M College of Pharmacy faculty members Nouri Neamati and Ashootosh Tripathi, and Theodora Danciu, a Clinical Associate Professor of Dentistry in the dental school’s Department of Periodontics and Oral Medicine. Also, children treated by residents in the dental school’s Graduate Pediatric Dentistry program will be part of the study, with researchers analyzing the oral biofilm of children with caries and those without, in an effort to understand differences in biofilm development.

Vesa Kaartinen, Associate Dean for Research at the School of Dentistry, notes that the major new grant is an example of the inter-disciplinary research that the University of Michigan has determined is a guiding principle in its latest Vision 2034 strategic plan that will inform the university’s future research strategy and investments. Kaartinen said the new RM1 grant fits well with the dental school’s longstanding commitment to leading dental, oral and craniofacial research. The grant’s emphasis on interdisciplinary researchers banding together on projects shows great promise for advancing scientific breakthroughs in many areas, none more important than reducing childhood caries, he said.

The grant, titled “A multiscale approach to develop and apply fluoride efflux inhibitors to reverse oral dysbiosis and eliminate early childhood caries,” is funded through June 2029. An abstract of the grant is available on the National Institutes of Health website.

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The University of Michigan School of Dentistry is one of the nation’s leading dental schools engaged in oral healthcare education, research, patient care and community service.  General dental care clinics and specialty clinics providing advanced treatment enable the school to offer dental services and programs to patients throughout Michigan.  Classroom and clinic instruction prepare future dentists, dental specialists and dental hygienists for practice in private offices, hospitals, academia and public agencies.  Research seeks to discover and apply new knowledge that can help patients worldwide.  For more information about the School of Dentistry, visit us on the Web at: www.dent.umich.edu.  Email: [email protected], or (734) 615-1971.