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The Forsyth Institute: More than a century of oral health innovation

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Dr. Wenyuan Shi

By Dr. Wenyuan Shi

Tue. 1 March 2022

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This guest editorial comes from Dr. Wenyuan Shi, Chief Scientific Officer and Chief Executive Officer of The Forsyth Institute – the only independent nonprofit research institute in the United States dedicated to investigating oral health and its connection to overall wellness. The Institute’s mission is to improve oral and overall health through innovative research, community outreach, and technological innovation.

Forsyth was founded in 1910 in Boston, Massachusetts, as the world’s first dental infirmary for children. The infirmary was the vision of the Forsyth family, who immigrated from Scotland to Boston in 1801 and made their fortune in the rubber industry. 

It all began when James Forsyth heard the cries of an impoverished child through the window of his hotel. He later learned from his dentist that many children suffered in pain from toothaches because they could not afford dental care. James and his family were determined to help these children. They donated millions of dollars to build and endow the Forsyth Dental Infirmary. Between 1914 and 1960, hundreds of thousands of Boston-area schoolchildren received comprehensive dental care and other medical treatments at Forsyth.

More about Forsyth’s history can be found here: https://www.forsyth.org/about-us/history/ 

Defining oral health

Scientists and clinicians at Forsyth pioneered the field of dentistry as we know it today. They were among the first to recognize that improving oral health would require treating the root causes of dental disease. As Forsyth evolved to focus on research, scientists at the Institute made some of the greatest impacts and discoveries in oral health, including:

• Starting one of the first two dental hygiene schools in the USA 

• Establishing the world’s first mobile dental program in 1920, thanks to a bus donation by the Kennedy family

• Discovering that cavities are an infection and identifying the specific bacterium that is the leading cause of dental decay (Streptococcus mutans)

• Elucidating the protective mechanisms of fluoride 

• Discovering that gum disease is episodic in nature, revolutionizing patient treatment 

• Identifying the bacterial complex that causes periodontal (gum) disease 

• Discovering “biofilms,” the structures that enable bacteria to adhere to hard surfaces 

• Gaining FDA approval for the first local oral antibiotic delivery system for the treatment of periodontal diseases (ActiSiteTM)

• Carrying out the first probiotic clinical studies on the bacterial replacement 

• Developing a novel anti-inflammation therapy against periodontitis 

• Founding the Human Oral Microbiome Database (HOMD) 

• Characterizing novel genes that cause bone loss 

• Identifying more than 700 species that colonize the human oral cavity, cultivating the “uncultivable.” 

• Identifying genes that cause human craniofacial birth defects.

• Completing the first oral pathogen genome project (Porphyromonas gingivalis)

• Leading part of the clinical trial linking P. gingivalis and gingipains from gum disease to Alzheimer’s disease

Building on a historical legacy

Today, Forsyth is grounded in a 3-pillared strategic plan focused on biological research, clinical service and public health outreach, and technological innovation. The ForsythKids mobile dental program continues the Institute’s founding mission by bringing dental care directly to thousands of children in underserved communities each year. Forsyth’s areas of research focus include inflammation and immunology, tooth formation, and microbiology, with particular historical expertise in the oral microbiome. 

Forsyth researchers led many of the first scientific studies of microorganisms in the mouth. They identified critical bacterial culprits that cause both cavities and periodontitis. These include Scardovia wiggsiae, which are highly associated with childhood caries, and Tannerella forsythia, the major periodontal pathogens, named in recognition of the Forsyth researcher who discovered them.

Researchers at Forsyth were pioneers of early translational oral microbiome technology. They developed the first FDA-approved local antibiotic to treat gum disease and the first FDA-approved probiotic therapy using genetically engineered Streptococcus mutans against tooth decay. 

One of Forsyth’s most significant and far-reaching contributions to the oral microbiology field is the Human Oral Microbiome Database, catalogs 775 microbial species from the human oral cavity. The scientists who built this database were part of a revolution in microbiology that used next-generation sequencing to identify and classify previously unknown and unculturable bacteria. The Human Oral Microbiome Database has been continuously funded by the National Institutes of Health for more than 20 years. It is used by scientists across the globe to advance our understanding of the oral microbiome and its role in health and disease. 

Scientists at Forsyth also developed a novel microscopy method known as CLASI-FISH that enables spectral imaging of up to 28 bacterial species at once. This approach allowed the world to see a visual representation of biofilms on the tongue for the first time, revealing where specific bacteria are located and the microbial communities they form.

Future directions

In an effort to deliver new oral health solutions to the public, Forsyth is investing in translational research and technology development. Forsyth dentech is the world’s leading oral health technology innovation conference convening thought leaders from industry, academia, and venture capital to accelerate innovation in the oral health space. 

The Forsyth Institute is an affiliate of the Harvard School of Dental Medicine, where many of our scientists and postdoctoral scholars hold joint appointments. Forsyth has been the training ground for thousands of researchers worldwide and is committed to educating the next generation of oral health champions. We offer in-person and virtual continuing education courses, internships and programming for middle, high school, and undergraduate students, and training opportunities in partnership with academic institutions across the country and abroad. 

Forsyth is now offering a variety of continuing education courses for dentists, including Innovative applications of TAD: From single tooth movement to skeletal open bite, offered virtually on March 10, 2022.

Recent high-impact publications

People with periodontitis are at higher risk of experiencing major cardiovascular events, according to recent research from Forsyth Institute and Harvard University scientists and colleagues. In a longitudinal study published recently in the Journal of Periodontology, Dr. Thomas Van Dyke, Senior Member of Staff at Forsyth, Dr. Ahmed Tawakol of Massachusetts General Hospital, and their collaborators showed that inflammation associated with active gum disease was predictive of arterial inflammation, which can cause heart attacks, strokes, and other dangerous manifestations of cardiovascular disease. Learn more.

In a recent study published in the Proceedings of the National Academy of Sciences, researchers from 41 institutions in 13 countries collaborated to reconstruct the oral microbiomes of Neanderthals, primates, and humans, including the oldest oral microbiome ever sequenced from a 100,000-year-old Neanderthal. Scientists analyzed fossilized dental plaque of humans and Neanderthals. They compared it to the plaque from chimpanzees, howler monkeys, and gorillas to better understand the evolutionary history of our oral bacteria. Floyd Dewhirst, Senior Member of Staff at the Forsyth Institute, was a co-author of the study. Learn more.

A group of bacteria called TM7 live in the human body by growing on the surfaces of other microbes, known as host bacteria. Ever since this arrangement was discovered, many scientists have assumed TM7 were harmful to humans, while their host bacteria were health-promoting. Studies have shown a higher abundance of TM7 in diseases including vaginosis, inflammatory bowel disease, and periodontitis, and a lower abundance of host bacteria, further suggesting TM7 are pathogenic. However, a new paper published today by Forsyth Institute researchers and colleagues finds the opposite effect—TM7 decreased periodontal inflammation and bone loss in a mouse model. The paper, Episymbiotic Saccharibacteria suppresses gingival inflammation and bone loss in mice through host bacterial modulation, was recently published in the journal Cell Host & Microbe. It describes the first time TM7 has been systematically cultured from human periodontal disease samples, isolated from their host bacteria, and studied in an animal model. Learn more. 

 Ongoing high-impact projects

In recent research, Forsyth Institute scientists in the Bor Lab and collaborators found that a group of bacteria called Saccharibacteria may protect humans against oral pathogens, upending the previously held belief that these microbes are disease-causing. This discovery opened up a whole new area of exploration in the field of microbiology, and the Bor Lab was granted a 5-year Research Project Grant (R01) from the National Institutes of Health to study these microbes further. Learn more.

The Forsyth Institute’s ForsythCares program was recently awarded a $50,000 grant to expand its services, providing oral health care to seniors in need. The funding will allow ForsythCares to create a “free-care fund” to bridge the cost deficit for seniors whose oral health treatment is not covered or insufficiently covered by MassHealth insurance. The ForsythCares pilot program aims to meet the oral health care needs of older adults—a population that often faces barriers to accessing adequate dental care. Learn more.

As a baby’s teeth begin to form in utero, they create growth lines that can vary in thickness depending on the mother’s wellbeing during pregnancy. One of these growth marks, called the neonatal line, is known to be thicker in children whose mothers experience poor nutrition, disease, and other types of physical stress, such as complicated labor or preterm birth. Since teeth keep a record of physical health, some scientists hypothesized that teeth could reveal clues about mental health as well. In a paper published recently in the journal Psychiatry, researchers describe their findings from a study of 70 shed primary teeth. The results show that babies whose mothers experienced stressful life events and mental health challenges during pregnancy developed thicker neonatal lines in their teeth than babies of mothers without those stressors. Babies whose mothers received social support during pregnancy had thinner neonatal lines. This project is an ongoing collaboration between The Forsyth Institute and Massachusetts General Hospital. Learn more.

More information can be found on forsyth.org, and by following The Forsyth Institute on InstagramTwitterLinkedIn, and Facebook. 

 

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