Symposium showcased NIDCR’s and NHLBI's past successes and current research
This year, NIDCR and the National Heart, Lung, and Blood Institute (NHLBI) observed 75 years as NIH institutes. To commemorate this milestone, the two institutes paired up to host the NHLBI and NIDCR Joint 75th Anniversary Symposium: The Science that Unites Us on May 22, 2024. The symposium covered the institutes’ histories, notable accomplishments, and overlapping areas of research.
Public Health Impact After 75 Years
Since its inception, NIDCR has driven research on topics such as the mouth’s microbiome, pain, head and neck cancer, tissue regeneration, craniofacial development, and the biology of saliva and the salivary glands. In terms of improving quality of life, Lawrence A. Tabak, D.D.S., Ph.D., Principal Deputy Director of NIH and former NIDCR Director, referred to NIDCR’s early research on fluoride and tooth decay as contributing to the most successful public health campaign in the history of the U.S.: Many people keep their teeth nowadays in part because of fluoridated drinking water. Aside from its significant influence on oral health, NIDCR-funded research has resulted in more than 60,000 scientific publications and 176 drugs that have been developed to treat a range of systemic conditions, including skin disease, cancer, infectious diseases, pain, neurological disorders, autoimmunity, inflammatory diseases, and others. Foundational studies of connective tissue, bone, and glands have allowed progress toward regrowing and restoring tissue function.
“An NIDCR legacy lies in public health impact driven by basic science that serves as a foundation for clinical research, which is then translated into clinical care and improved quality of life,” said NIDCR Deputy Director Jennifer Webster-Cyriaque, D.D.S., Ph.D.
As for NHLBI, numerous achievements in heart, blood, lung, and sleep research have resulted in millions of lives saved and improved. This includes public health recommendations and medications that have resulted in a 70% reduction in deaths from cardiovascular disease alone. NHLBI’s advances in blood diseases such as sickle cell anemia and lung diseases like cystic fibrosis — once fatal childhood diseases — now allow people to live well into middle age.
“As for return on investment, NHLBI is a poster child on investing in biomedical research,” said Gary Gibbons, M.D., Director of NHLBI. “A key component of our work has been its crosscutting nature, in that studies like Framingham [Heart Study] have provided insights on osteoporosis, dementia, and stroke, as well.”
“I look forward to the 100-year celebration to see how much more we can accomplish together,” said Dr. Tabak.
The Oral-Systemic Connection: Viral Infections
Much of the overlap between NIDCR’s and NHLBI’s research lies in the oral-systemic connection – the idea that the health of the mouth affects the health of the rest of the body, and vice versa. During the symposium, a common thread on this topic pertained to viral infections. Although these infections can be systemic, viral infections such as HIV, Epstein-Barr virus, and cytomegalovirus are worsened by poor oral health and periodontal disease. Other viral infections, such as herpes, influenza, or SARS-CoV-2, can be transmitted through the mouth.
Enteric viruses
“Stomach flu” viruses, or enteric viruses such as rotavirus, norovirus, and astrovirus, typically cause uncomfortable digestive symptoms in adults and older children. However, these viruses can be life-threatening to children and babies under 5 years old, older adults, and people with weakened immune systems. Until very recently, these infections were thought to spread primarily by ingestion of fecal matter through improper handwashing. NHLBI Senior Investigator Nihal Altan-Bonnet, Ph.D., presented findings on her team’s collaboration with former NIDCR Senior Investigator Matthew Hoffman, B.D.S., Ph.D., and NIDCR Acting Deputy Scientific Director John Chiorini, Ph.D., using mother-pup mice pairs to study viral spread. The dual-institute team found that in addition to the fecal-mouth route, norovirus and rotavirus could spread from nursing pups to the mammary glands of the mother through the pups’ saliva. They also found that the saliva was much more infectious than the fecal matter. If the findings bear out in human studies, experts may need to modify public health recommendations to curb spread.
HIV, HPV, and Head and Neck Cancer
Multiple human papillomavirus (HPV) strains are known to increase the risk of cancer, with the HPV-16 strain most likely to cause cervical, vaginal, oral, and head and neck cancers. People with weakened immune systems may be at higher risk of developing HPV-related cancers. Gypsyamber D’Souza, Ph.D., M.S., M.P.H., a professor of epidemiology at the Johns Hopkins University, evaluated HPV infection in a group of men and women with HIV. Her team observed that people with HIV were more likely to have oral HPV infection than people without HIV. They also found that the prevalence of oral HPV in people with HIV increased the more suppressed the person’s immune system was.
HPV infections typically take a year or two to resolve or go dormant in healthy adults. Yet for more than 1,800 people with HIV in the study, oral HPV infections took an average of four years to clear. Men were less likely to clear the virus, and clearance decreased with age. People with HIV and persistent oral HPV infections, and particularly those infected with the HPV-16 strain, may be among those at the highest risk for developing head and neck cancer, according to Dr. D’Souza. Of the study participants, two men have already developed HPV-related head and neck cancer. Although there’s a vaccine for HPV that is preventive, currently there is no treatment.
HIV and the Oral Microbiome
Although Streptococcus mutans bacteria are major drivers of cavities, more than 700 other microbial species can be detected in the mouths of people with tooth decay. People with periodontal disease or tooth decay are also more likely to harbor disease-causing bacteria in their mouths. These pathogens can travel to other sites in the body and are linked to systemic diseases like diabetes, lung disease, or even cancer.
Speaker Apoena De Aguiar Ribeiro, D.D.S., Ph.D., M.S., a research associate professor at the University of North Carolina Chapel Hill, shared findings from an analysis of the mouth’s microbiome in people with HIV. These research participants were three times more likely to have lost all their teeth compared to the national average and were more likely to have untreated tooth decay. When it came to the mouth microbiome, Dr. Ribeiro found that inflammation and HIV infection reduced microbial diversity as well. These findings suggest that an imbalance in the microbiome may serve as a biomarker of disease severity in HIV. The team will assess links among the oral microbiome findings, heart disease, lung disease, and other systemic diseases.
Oral Health and Cardiovascular Disease
Seventy-five years ago, the newly formed NHLBI launched the Framingham Heart Study to understand the causes and risk factors for cardiovascular disease. The study followed more than 75,000 people over three generations. Among the findings was the discovery that diabetes, obesity, physical activity, diet, and high blood pressure contribute to one’s risk of cardiovascular disease.
Later, the NHLBI-funded Atherosclerosis Risk in Communities study linked periodontal disease with heart attack and stroke. Speaker James D. Beck, Ph.D., the W.R. Kenan Distinguished Professor at the University of North Carolina, detailed his and others’ decades of work to further cement the relationship, much of which is covered in the NIDCR news article Healthy Mouth, Healthy Body. Over the years, researchers realized that many of the same risk factors for cardiovascular disease contribute to periodontal disease risk as well.
The cardiovascular-periodontal connection was a common thread in the day’s discussion. NHLBI Director Dr. Gibbons separately expounded on the extent of this relationship, explaining that C-reactive protein — an indicator of inflammation — is also linked to both conditions. He discussed additional research demonstrating that blocking the inflammation-promoting protein interleukin-1β reduced inflammation and heart attacks in animals and humans. Dr. Gibbons said that there’s evidence that targeting this same inflammatory process could also change the microbiome and affect other inflammatory diseases, which could include periodontal disease.
Whole Person Health for Everyone
“Dental health is a canary in the coal mine,” said Leith J. States, M.D., M.P.H., Chief Medical Officer of the Office of the Assistant Secretary for Health and Acting Director of the Office of Science and Medicine at the Department of Health and Human Services (HHS). “Oral health is a reflection of [a person’s] socioeconomic status, who they are, and their whole person health.”
Dr. States said he’s observed that simple interventions such as preserving or replacing missing or damaged teeth can bring about a vast improvement in quality of life and give people the capacity and confidence to reengage with their community. At HHS and NIH, he said, clinicians are committed to caring for the whole person, not just treating a disease or a symptom.
Oral Health Disparities
However, not everyone has reaped the benefits of these medical advances over the years. Symposium speaker Louis W. Sullivan, M.D., former secretary of HHS, challenged researchers and clinicians at NIH to close the gaps between the affluent and poor, and among White, Black, Native American, and Pacific Islander populations. He said that equity must improve, and that NIH-driven medical advances must not become tools that widen discrepancies. He encouraged investigators to increase racial and gender representation in research, improve trust in health care, and advocate through good communication, honesty, and integrity.
Dr. Sullivan pointed to a campaign launched in Alaska as an example of a successful effort to address health disparities. Around 30 years ago, to tackle the shortage of dentists in Alaska, a program was launched to train dental therapists in the state. More than 50 million people in the U.S., about 16% of the population, live in a place with a shortage of dentists. Dental therapists provide basic dental services and require less training than a traditional dentist. Critics of the program feared the quality of care would decline. However, due to the success of the Alaska campaign, 12 additional states have now enacted these training programs to improve access to oral health care across the U.S.
NIDCR Director Rena D'Souza, D.D.S., M.S., Ph.D., emphasized the importance of building a more equitable and accessible oral health care ecosystem. In a prerecorded video shown during the symposium, she said, “We must translate scientific discoveries into treatments and care that everyone can access, not just the privileged. In parallel, we must build an oral health workforce that represents everyone in our nation.”
She called attention to NIH’s 2021 report, Oral Health in America: Advances and Challenges, which showed that people from marginalized groups face higher burdens of oral disease and lack access to safe, high quality, and affordable dental care.
Dr. D’Souza said that technological advances could allow experts to solve previously intractable problems in oral health, including health disparities. She predicted that advances in 3D printing technologies will make dental implants and dentures cheaper, which will make care more affordable and accessible. She also said that integrating medical and dental records will better allow clinicians to provide more holistic health care that can benefit patients with multiple health conditions, like those experienced by people in medically underserved populations. Data science will enable better tracking of oral health trends to target interventions toward the communities most affected by a given disease.
Cardiovascular Health Disparities
Dr. Gibbons addressed similar disparities in cardiovascular health and discussed how NHLBI is working to tackle the problem. For example, the NHLBI-funded SPRINT clinical trial changed medical practice, demonstrating that aiming for a systolic blood pressure number (the top number) of 120 or less can decrease the burden of heart attacks or heart failure and death. Yet, many communities still have poor rates of blood pressure control. To combat this, an NHLBI-funded study focused on community engagement in barber shops, where men frequently gather. The researchers trained barbers to engage in blood pressure measurement and to spread the message that high blood pressure could be a “silent killer.” This method was effective at spreading awareness and encouraged men to stick with their blood pressure treatments.
Another condition that disproportionately affects certain populations — and is a major priority for NHLBI — is high blood pressure in pregnancy, or preeclampsia, said Dr. Gibbons. Preeclampsia can lead to underweight or premature newborns, stillbirths, and a higher risk of complications in the mother, such as excessive bleeding and even death. Black and Latina women have a two-to-four-times higher risk of developing preeclampsia than White women. Additionally, pregnant women with periodontal disease are more likely to have preeclampsia than women without gum disease, and they also are more likely to have babies born underweight, prematurely, or stillborn. Toward that end, NHLBI hopes to identify the people most at risk of preeclampsia. Dr. Gibbons said scientists are using continuous blood pressure monitoring, artificial intelligence, and machine learning to measure slight variations in blood pressure or changes in the vasculature that could be predictive of preeclampsia. And it’s possible that oral health may factor into these calculations.
“As we enhance our ability to predict, we can use more precise precision medicine to identify those at greatest risk, anticipate and reduce that risk, or at least initiate treatment earlier in pregnancy,” said Dr. Gibbons.
He expressed excitement about the Chronic Hypertension in Pregnancy study. Study researchers treated chronic high blood pressure with medication, lowering it more than most clinicians typically push for, which in turn reduced preeclampsia risk. Within a month of the study’s implementation, the strong findings had already led to adjusted recommendations in clinical practice to help reduce maternal deaths. Dr. Gibbons said that he wants to make sure that the benefits of that science reach the communities that need it most.
Related Links
- Healthy Mouth, Healthy Body
- Facing Cancer Head-On
- Exploring the Mouth’s Microbial Wonders
- Resolution Honoring NIDCR’s 75th Anniversary Passed in U.S. Senate
References
- Ghosh S, Kumar M, Santiana M, Mishra A, Zhang M, et al. Enteric viruses replicate in salivary glands and infect through saliva. Nature. 2022 Jul;607(7918):345-350. doi: 10.1038/s41586-022-04895-8.
- Beachler DC, Weber KM, Margolick JB, Strickler HD, Cranston RD, et al. Risk factors for oral HPV infection among a high prevalence population of HIV-positive and at-risk HIV-negative adults. Cancer Epidemiol Biomarkers Prev. 2012 Jan;21(1):122-33. doi: 10.1158/1055-9965.EPI-11-0734.
- D'Souza G, Tewari SR, Troy T, Webster-Cyriaque J, Wiley DJ, et al. Oncogenic Oral Human Papillomavirus Clearance Patterns over 10 Years. Cancer Epidemiol Biomarkers Prev. 2024 Apr 3;33(4):516-524. doi: 10.1158/1055-9965.EPI-23-1272.
- Rosa TDC, Neves ADA, Azcarate-Peril MA, Divaris K, Wu D, et al. The bacterial microbiome and metabolome in caries progression and arrest. J Oral Microbiol. 2021 Jun 16;13(1):1886748. doi: 10.1080/20002297.2021.1886748.
- Yang L, Dunlap DG, Qin S, Fitch A, Li K, et al. Alterations in Oral Microbiota in HIV Are Related to Decreased Pulmonary Function. Am J Respir Crit Care Med. 2020 Feb 15;201(4):445-457. doi: 10.1164/rccm.201905-1016OC.
- Beck JD, Papapanou PN, Philips KH, Offenbacher S. Periodontal Medicine: 100 Years of Progress. J Dent Res. 2019 Sep;98(10):1053-1062. doi: 10.1177/0022034519846113.
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