Bacteria play a significant role in oral health, whether it’s related to gingivitis or tooth decay. But for Dr. Shareef Dabdoub, assistant professor in the Department of Periodontics and the Division of Biostatistics and Computational Biology at the University of Iowa College of Dentistry, viruses may play an equally or perhaps more important role in understanding oral health.

In 2024, Dabdoub received an NIH R03 grant to investigate the oral virome, the vast population of viruses inhabiting the mouth. Although the oral microbiome has been studied extensively, the viral component remains largely uncharted. “Viruses have been overlooked primarily because they’re hard to study,” Dabdoub explains. “Unlike bacteria, which can often be cultured and identified through common genetic markers, viruses lack similar universal marker genes. Until recently, the technology to study them at scale simply wasn’t available.”

Advances in high-throughput sequencing have changed that, enabling researchers to capture the full genetic picture of oral samples. Yet challenges remain. “When we sequence saliva or plaque, most of what we get is human DNA,” says Dabdoub. “We can lose up to 90 percent of the data just filtering that out. And viruses make up only about five to ten percent of the biomass, so every bit of information matters.”

Despite these hurdles, early findings suggest that viruses, especially bacteriophages, may play a critical role in oral health. Bacteriophages are viruses that infect bacteria. “We know there are ecological shifts in viral populations between health and disease,” Dabdoub says. “Some viruses appear more often in periodontal disease than in healthy sites. But we don’t yet understand their function or how they may influence disease progression.”

That knowledge gap is what makes this research so compelling. In a single sample, Dabdoub’s team may find thousands of viruses, roughly ten times more than the typical number of bacterial species. “The battle between bacteria and viruses has been going on far longer than our battle with bacteria,” he notes. “Bacteria have evolved defense systems to fight off phages and phages have co-evolved anti-defense mechanisms. Understanding these interactions could open new doors for treatment.”

One promising avenue is phage therapy, that is, using viruses to target harmful bacteria. “Many antibiotics are broad-spectrum, which means they wipe out both harmful and beneficial bacteria,” Dabdoub explains. “Phages, on the other hand, are highly specific. If we can identify which phages target disease-associated bacteria, we could develop therapies that restore balance more effectively with fewer side effects.” Such precision could be especially valuable in the oral cavity, where disease often results from shifts in microbial communities rather than the arrival of foreign pathogens.

To make sense of the enormous datasets generated by metagenomic sequencing, Dabdoub employs advanced computational tools, including machine learning. “Deep learning approaches are incredibly useful for identifying viral genomes,” he says. “Viruses evolve rapidly and often borrow genes from bacteria, so traditional database matching doesn’t work well. Machine learning can detect patterns and predict which sequences belong to viruses, even those we’ve never seen before.”

His team also uses ensemble models to predict virus-host relationships, a critical step toward understanding how phages interact with bacteria. “Knowing which viruses pair with which hosts helps us explore therapeutic potential,” Dabdoub says.

Looking ahead, Dabdoub envisions a future where oral health research integrates multiple layers of data, including DNA, RNA, proteins, and metabolites, to capture a complete picture of disease processes. “We need to move beyond identifying who’s there to understanding what they’re doing and how that fits into a systemic picture,” he says. “Combining genomics with transcriptomics and other approaches will give us an end-to-end view of how viruses, bacteria, and the immune system interact.”

For now, his work is laying the foundation for that future and for a new era in oral health research. “The oral virome is a frontier,” Dabdoub says. “We’re just beginning to understand its complexity, but the potential impact on patient care is enormous.”