What Dentists Need to Know About The Oral Virome

For most of the past two decades, the oral microbiome conversation in dentistry has been about bacteria. The October cover story in JADA argues that the oral virome, the viruses living alongside those bacteria, belongs in that conversation, and a $20.6 million NIH center led by UCLA's dental school is now mapping it.

TL;DR

• UCLA's School of Dentistry leads a $20.6 million NIH center mapping viruses across the oral–gut–brain axis.

• Bacteriophages, which infect bacteria, make up most characterized oral viruses and may shape plaque ecology.

• Early data link a distinct oral virome, including redondoviruses, to periodontitis, though causation is unproven.

• No virome test or phage therapy is ready for the operatory, and current caries and periodontal care stand.

Why Is JADA Putting Viruses On Its Cover?

The October 2026 issue of JADA leads with "Oral Virome in Health and Disease," a review by Yvonne Hernandez-Kapila, DDS, PhD, associate dean of research at the UCLA School of Dentistry, with colleagues from UCLA, Charité Berlin and USC. It belongs to the journal's Oral Science Trends series of invited reviews on where biomedical science may change clinical care.

The review doubles as a progress report. Hernandez-Kapila is the contact principal investigator of the NIH Human Virome Characterization Center for the Oral-Gut-Brain Axis, funded with $20.6 million over five years in 2025. It is the largest NIH grant in the dental school's 60-year history and the only one of the program's five centers based at a dental school.

For clinicians, the pitch will sound familiar. Dentistry spent two decades learning to see caries and periodontitis as diseases of whole microbial communities. The review asks whether viruses, especially the bacteriophages that prey on oral bacteria, are a missing layer of those communities.

What Exactly Is The Oral Virome?

The oral virome is the full set of viruses in the mouth, and clinicians already know some of its members well. Herpes simplex virus causes cold sores, Epstein-Barr virus and cytomegalovirus turn up in periodontal lesions, and HPV-16 is found in roughly 90% of HPV-positive oral cancers, which is one reason the ADA's 2026 oral cancer screening guidelines keep the clinical exam central. Most characterized oral viruses, however, are bacteriophages, or phages, which infect bacteria and cannot infect human cells.

The scale is easy to underestimate. A milliliter of saliva carries roughly 100 million virus-like particles, about ten times the density of seawater, and estimates for the whole body exceed 380 trillion viruses. Viral DNA in a saliva sample is the normal state of a healthy mouth and says nothing, on its own, about infection.

How Does The Virome Fit Into The Oral Microbiome?

The two terms overlap. "Microbiome" covers every microorganism in a site along with its genes, though in dentistry it usually means bacteria. The virome is the viral slice of that same community, living in the same dental plaque, saliva, and soft tissue.

Every group in the table interacts with the others, so the virome cannot be studied in isolation from the bacteria that many of its members depend on.

Why Do Bacteriophages Matter For Plaque Ecology?

A bacteriophage attaches to a specific bacterial host and injects its genome. Some phages multiply and burst the cell, while others integrate into the bacterial chromosome and travel with it for generations. That behavior gives phages several ways to shape a biofilm:

• Which bacterial strains survive and which shrink

• How bacteria compete for space and nutrients

• How genes, including some resistance genes, move between bacteria

• How biofilms form, thicken or break apart

• How stable a community stays over time

The arms race between phages and bacteria is old enough that CRISPR, the bacterial defense now famous as a gene-editing tool, evolved partly to fend them off, and dental plaque bacteria carry those defenses too. If phages help decide which species thrive in plaque, they add a layer to the ecological model of caries and periodontitis that dentistry already uses. No study has yet shown that phages cause or prevent either disease.

Why Has Oral Microbiology Focused On Bacteria For So Long?

For most of the 20th century, culture determined what researchers could study, and the organisms that grew readily in a dish dominated the story: Streptococcus mutans for caries and Porphyromonas gingivalis for periodontitis. Viruses, which need living host cells and form no colonies, were largely invisible to that approach.

Sequencing changed the question. The NIH Human Microbiome Project, which ran from 2007 to 2016, built reference sets for microbial genomes and moved the field from single pathogens toward whole communities. The JADA review treats the virome as the next step, shifting the question from which bacteria are present to how viruses shape the entire system.

What Is The NIH Human Virome Program Doing?

The NIH Common Fund created the Human Virome Program to catalog the viruses that live in healthy people, develop better tools for studying them, and define their role in health and disease. Five characterization centers share the work, based at the University of Pennsylvania, Vanderbilt, the Broad Institute, Stanford, and UCLA.

UCLA's center focuses on the oral–gut–brain axis. NIH announced the $20.6 million grant in February 2025, and the discovery team spans UCLA, Baylor College of Medicine, Mayo Clinic, UC San Diego, USC, Penn State, and the NIDCR.

Which Oral Samples Is The UCLA Center Collecting?

The center plans virome atlases for a wide range of oral specimens, some of them at single-tooth resolution:

• Saliva and oral swabs

• Dental plaque and extracted teeth

• Gingival tissue and gingival crevicular fluid

• Tears and nasopharyngeal swabs

The team will align that oral data with gut samples such as stool and colorectal tissue, with brain tissue and cerebrospinal fluid, and with blood, skin swabs and breast milk. It expects to profile thousands of biospecimens to build standardized reference datasets for healthy people across age groups and ethnic backgrounds.

How Are Viruses Identified In An Oral Sample?

Every oral sample mixes human cells with bacteria, fungi, archaea, and viruses, and labs extract all of the DNA and RNA together. Viral capture enrichment can then pull out viral sequences before next-generation sequencing, or shotgun metagenomic sequencing can read everything and sort the viral reads computationally afterward.

The complication is that many reads match nothing in existing databases. Researchers call these sequences viral "dark matter," and building better reference catalogs is one of the program's central aims.

What Is The Oral–Gut–Brain Axis?

The mouth connects to the rest of the body through several routes. Swallowed saliva carries oral microbes into the gut all day, inflamed periodontal tissue lets microbial products into the circulation, and immune and neural signals run in both directions. Researchers study links along a chain:

1. Oral microbial communities

2. Gut microbial communities

3. Immune and metabolic signaling

4. Possible effects in distant organs, including the brain

Most of this work has focused on bacteria, including mouse studies tying periodontal disease to Alzheimer's-like brain inflammation. The UCLA center extends those questions to viruses, and the JADA review notes that viruses have been found in cerebrospinal fluid, long assumed to be sterile. These remain associations under investigation, and no study shows that oral viruses cause brain disease.

Could The Virome Help Explain Periodontitis?

Viruses are not new to periodontology. Herpesviruses such as Epstein-Barr virus and cytomegalovirus have been studied in periodontal lesions for years, and a 2026 review in the Journal of Periodontal Research, co-authored by Hernandez-Kapila, examines links between viruses, periodontitis and systemic disease. The disease itself develops from microbial dysbiosis combined with the host immune-inflammatory response, the framework behind current periodontal staging and grading.

The JADA review adds two observations. Data from patients and animal models point to a distinct disease-associated oral virome, and redondoviruses, small circular DNA viruses found in saliva and gingival areas, show a strong association with periodontitis. That leaves several open questions:

• Do viral communities shift as periodontitis develops?

• Do phages change the balance of periodontal bacteria?

• Do viruses amplify inflammation in the gingiva?

• Could a viral signature mark active disease?

The last question has the most immediate clinical relevance. A viral signature could describe the microbial environment of a pocket long before anyone proves that a virus causes the disease.

What About Caries?

Caries is a biofilm-mediated, diet-modulated disease in which frequent sugar shifts plaque toward acid-producing, acid-tolerant bacteria, a process detailed in our overview of cavity signs and stages. If phages shape bacterial ecology, they may change alongside cariogenic biofilms and could, in principle, influence which species dominate. Researchers want to know:

• Do healthy and caries-active mouths carry different phage communities?

• Can specific phages infect Streptococcus mutans or other acid producers?

• Could viral signatures flag ecological shifts before a lesion appears?

• Could phage manipulation someday change biofilm behavior?

The last idea is highly experimental, and no phage-based caries treatment exists for patients. For now, the virome offers a hypothesis about caries ecology, and clinical management is unchanged.

Could Saliva Become A Diagnostic Window Into The Virome?

Saliva is easy to collect and carries material from the teeth, gingiva, tongue, and oropharynx. Most human oral virome data so far come from saliva, with only limited data from dental plaque, and the JADA authors describe oral specimens as well suited to future chairside viral diagnostics. Salivary biomarker research already targets:

• Oral disease activity

• Gingival inflammation

• Shifts in microbial communities

• Signals of systemic health

A future salivary test might read bacterial and viral signatures from a single sample. That remains a research direction, and no saliva-based virome test is in routine dental use.

Could Oral Viruses Become Disease Biomarkers?

A useful biomarker is a measurable signal tied reliably to a biological state. A viral marker would first need to track with disease across many patients, and it would then need to hold up across:

• Ages and life stages

• Populations and geographic regions

• Health conditions and medications

• Diets and oral hygiene habits

• Different stages of oral disease

An abnormal signature only makes sense against a known normal range, which is why the Human Virome Program starts with healthy people.

Why Is Defining A Healthy Oral Virome So Hard?

The oral environment changes constantly, and many variables may shift viral communities from one visit to the next:

• Age, diet, and geography

• Oral hygiene and smoking

• Medications, especially antibiotics

• Immune status and systemic disease

• Saliva flow and dry mouth

• Periodontal and caries status

Xerostomia alone alters the whole ecosystem. Earlier saliva studies found oral viruses to be personal and fairly persistent within each person, which helps longitudinal tracking yet makes population norms harder to set.

The technical problems are just as real. Virus taxonomy keeps changing, with the International Committee on Taxonomy of Viruses recently abolishing several long-used phage families, and there is still no universal consensus on virome methods.

Could Phages Become Dental Therapeutics?

Phage therapy uses selected phages to kill specific bacteria. It was first tried in the early 20th century, faded as antibiotics took over Western medicine, and has returned as an option for multidrug-resistant infections.

In dentistry, a targeted phage could in theory act more precisely than broad agents such as chlorhexidine. Potential targets include:

• Periodontal pathogens

• Acid-producing caries bacteria

• Bacteria in endodontic infections

• Biofilms around dental implants

The oral biofilm holds hundreds of interacting species, and removing one can open space for another. The JADA authors also float beneficial "provirotics" and oral virome transplants as long-range ideas, and none of these approaches is close to clinical use.

What Could Virome Research Eventually Change In Practice?

If reproducible viral signatures hold up, the research path runs through four stages:

1. Map healthy oral viruses

2. Identify changes linked with disease

3. Validate reproducible viral signatures

4. Test clinical uses, from biomarkers to targeted therapy

Each potential application below is speculative, and none is a current clinical standard.

The JADA authors expect virome data to inform caries and periodontal status and, eventually, predictions of future oral health risk. None of these applications replaces established diagnosis, prevention, or periodontal care today, and each depends on the healthy baseline the Human Virome Program is still building.

What Do Researchers Still Not Know?

The field is young enough that some of its most basic questions remain open. Six of them stand out:

• What a healthy oral virome looks like across ages and populations

• How stable one person's virome stays over months and years

• Which disease associations are causal and which involve bystanders

• How much geography and lifestyle shift baseline communities

• Whether viral signatures can predict disease in prospective studies

• Whether manipulating the virome is safe for the wider ecosystem

The JADA authors stress that functional assays will be needed to separate correlation from causation.

What Does This Mean For Dental Practice Today?

Nothing in the JADA review changes chairside protocols, and no dentist needs to test a patient's virome. What it changes is the frame. Dentistry has moved from single pathogens to microbial ecosystems and host responses, and the virome adds another layer to that model while plaque control, fluoride, periodontal therapy, and regular recall remain the basis of care.

Patients may begin asking about the oral virome as coverage spreads, and a clear answer helps. Viruses are a normal part of a healthy mouth, most of them infect bacteria, and research into what they do is only beginning. The next advance in oral microbiome science may well come from the viruses living alongside, and sometimes inside, its bacteria.

Bottom Line

The October 2026 JADA cover story and a $20.6 million NIH center at UCLA put the oral virome on dentistry's research agenda. Most oral viruses are bacteriophages that may shape plaque ecology, and early data tie a distinct virome to periodontitis without proving cause. Salivary virome tests and phage therapies remain research ideas, so current caries and periodontal care stand unchanged.