Could the bacteria in your mouth one day protect you from cavities as effectively as brushing or flossing?
Wenjun Zhang, a professor of chemical and biomolecular engineering at the University of California, Berkeley, believes so. Her team is working to harness “good” oral bacteria and strengthen their ability to outcompete cavity-causing microbes, paving the way for a new generation of probiotic oral health therapies.
The human mouth hosts hundreds of bacterial species that collectively form dental plaque. While many of these microbes are linked to tooth decay through their acid-producing activity, scientists have learned that not all bacteria — or even all strains of the same species — behave the same. Some are harmful, others harmless, and some potentially beneficial.
Rather than focusing solely on bacterial species, Zhang’s team analyzes the DNA of entire oral microbial communities — known as the metagenome — to identify gene clusters tied to dental disease.
In findings published August 19 in the Proceedings of the National Academy of Sciences, Zhang and her colleagues reported the discovery of a gene cluster that produces two molecules enabling bacteria to form resilient biofilms on teeth. These sticky biofilms can promote decay when built by harmful bacteria, but Zhang sees an opportunity to transfer the gene cluster to beneficial strains to help them establish a stronger foothold and crowd out cavity-promoting microbes such as Streptococcus mutans.
“Strains belonging to the same species can act as pathogens, harmless commensals, or even probiotics,” Zhang explained. “If we can give beneficial bacteria the ability to build strong biofilms, they could outcompete the harmful ones.”
The work, supported by the National Institute of Dental & Craniofacial Research, highlights the overlooked role of specialized bacterial metabolism in shaping oral health. Graduate student McKenna Yao and colleagues identified the gene cluster by analyzing vast databases of oral metagenomes, then pinpointed the small molecules it produces. One molecule acts like glue, clumping cells together, while the other works like string, forming chains — together creating the sticky biofilm layer on teeth.
Zhang and her team call these newly discovered molecules “mutanoclumpins.” Though they can promote cavity formation in some contexts, they might also be repurposed to strengthen oral probiotics such as Streptococcus salivarius, which is already marketed as a supplement but struggles to form durable biofilms.
The research underscores the broader health potential of microbial “secondary metabolites” — specialized molecules produced by bacteria that influence their survival and interactions. Such compounds have already yielded antibiotics in soil microbes, and Zhang believes oral bacteria may hold similar promise for human health.
Future research will focus on mapping these metabolites across the oral microbiome, identifying both harmful molecules to block and beneficial ones to enhance.
Still, Yao emphasized that tooth brushing remains the most reliable way to disrupt biofilms today. “We think there may be better ways in the future,” she said, “but we’re just beginning to understand the complexity of the mouth’s microbial community.”
The study’s co-first authors are Berkeley graduate students Nicholas Zill, Colin Charles Barber, and Yao. Additional collaborators include Yongle Du, Rui Zhai, Eunice Yoon, Dunya Al Marzooqi, and visiting scholar Peijun Lin.
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