Artificial intelligence for early detection of gum inflammation

 

IMAGE: THREE CASES ILLUSTRATING DENTIST'S VISUAL EXAMINATION (B) AND AI'S DETECTION (C) OF GUM PROBLEMS (A) INTRAORAL PHOTOGRAPH (B) HEALTH STATUS LABELLED BY A CALIBRATED DENTIST (GREEN=HEALTHY, RED=DISEASED, YELLOW=QUESTIONABLE) (C) AI DETECTION RESULTS view more 

CREDIT: FACULTY OF DENTISTRY, THE UNIVERSITY OF HONG KONG

A groundbreaking study led by researchers at the Faculty of Dentistry of the University of Hong Kong (HKU), in collaboration with multiple international institutions has successfully demonstrated the use of artificial intelligence (AI) in detecting gum inflammation, also known as gingivitis, from intraoral photographs.

This cutting-edge technology can revolutionise early detection and prevention of oral and systemic diseases linked to gum inflammation, such as tooth loss, cardiovascular diseases, and diabetes.

The study, published in the prestigious International Dental Journal, an official journal of the World Dental Federation (FDI), shows that AI algorithms can analyse patients' intraoral photographs to detect signs of inflammation like redness, swelling, and bleeding along the gum margin with over 90% accuracy, matching the visual examination of a dentist. This innovative technology enables population-wide monitoring of gum health and paves the way for more personalised dental care.

The study was conducted by researchers from the HKU Faculty of Dentistry, the Department of Computer Science at Hong Kong Chu Hai College, the School of Information Engineering at Guangdong University of Technology, and the Faculty of Dentistry at The National University of Malaysia. It involved developing and testing an AI model using a dataset of over 567 images of gums with varying degrees of inflammation and is one of the first to explore the use of AI in detecting gum inflammation.

Dr Walter Yu-Hang Lam, the study’s leading HKU researcher, emphasises the significance of the findings for the early detection and management of gum disease.

"Many patients do not attend regular dental check-ups, and they only seek dentists to alleviate pain when their teeth are at the end stage of dental diseases, in which tooth loss is inevitable, and only expensive rehabilitative treatments are available. Our study shows that AI can be a valuable screening tool in detecting and diagnosing gum disease, one of the key indicators of periodontal disease, allowing earlier intervention and better health outcomes for the population." He said.

The use of AI in dentistry has been gaining momentum in recent years, with researchers exploring various applications of the technology, from detecting cavities to predicting treatment outcomes to biomimetic design of artificial teeth. The use of AI in gum inflammation detection is a promising development that could revolutionize how gum disease is detected, treated, and even prevented.

Dr. Reinhard Chun-Wang Chau, an HKU co-investigator of the team, pointed out the benefits of using intraoral photographs in conjunction with AI technology and said: “Based on these intraoral photographs, patients can address the area that they did not clean well and seek dentist’ help at an earlier stage.”

The collaborative nature of this study is a testament to the power of interdisciplinary research and knowledge exchange. By bringing together experts from different fields and regions, the researchers can develop an AI model that could accurately detect gum inflammation, with important implications for public health and wellbeing.

For the project’s next stage, Dr Lam plans to utilize the AI system for community services, making the technology more accessible to elderly and underserved communities, with the aim of improving oral health outcomes and reducing health disparities.

The study, Accuracy of Artificial Intelligence-Based Photographic Detection of Gingivitis, is available on the International Dental Journal
(https://doi.org/10.1016/j.identj.2023.03.007).

American Dental Association releases new tooth decay treatment guideline

Expert panel advises conservative approaches in first-ever restorative clinical recommendations for removal of tooth decay

Peer-Reviewed Publication

AMERICAN DENTAL ASSOCIATION

CHICAGO, June 26, 2023 – A new American Dental Association (ADA) clinical practice guideline suggests conservative methods to treat tooth decay in primary and permanent teeth could lead to better outcomes when used with common restorative materials like fillings or caps. An expert panel of dentists developed the first-ever guideline on this topic after extensive review of approximately 300 published studies.

The guideline, published in the July issue of The Journal of the American Dental Association, contains 16 recommendations regarding treatment of moderate and advanced tooth decay in primary and permanent teeth that have not received endodontic treatment, such as a root canal. It indicates conservative carious tissue removal (CTR) – in which a dentist removes infected tissue while preserving as much of the original tooth structure as possible – is less likely to result in adverse outcomes like nerve exposure or a failed filling. 

The recommendations also identify selective CTR as an effective treatment option in most cases of moderate or advanced decay in primary and permanent teeth. This method involves removing most, but not all, of the decayed tissue before sealing the tooth with a filling or cap. The bacteria left behind under the new filling or cap no longer has what it needs to multiply, which stops tooth decay.

Additionally, the guideline affirms the efficacy of the most common restorative materials for treating moderate or advanced tooth decay, such as tooth-colored fillings, silver-colored fillings (amalgam) or preformed caps in children. It suggests specific materials for primary and permanent teeth depending on the extent of the decay.

Lead author Vineet Dhar, B.D.S., M.D.S., Ph.D., is clinical professor and chair of orthodontics and pediatric dentistry at the University of Maryland School of Dentistry and a member of the ADA Council on Scientific Affairs. He said the recommendation encapsulates restorative dentistry’s two main objectives: maintaining healthy tooth structure and protecting the soft tissue inside the tooth.

“While research had already confirmed that selectively removing decayed tissue is an effective approach to treating early tooth decay, dentists needed an evidence-based guideline to provide them with a range of treatment choices for patients with moderate to advanced tooth decay,” Dr. Dhar said. “These recommendations can now inform restorative care strategies in the U.S. and on a global level.”

This is the ADA’s second clinical practice guideline in a series on caries treatment. The new guideline was developed by the ADA Council on Scientific Affairs and the Clinical and Translation Research team within the ADA Science and Research Institute, which convened a panel of experts to review the best-available scientific evidence around treatments and materials. The new restoration guideline and existing recommendations on non-restorative treatment for tooth decay can be found at ada.org/cariesguidelines.

NJew bacterial species involved in tooth decay

 

Large study in children reveals Selenomonas sputigena as a key partner of Streptococcus in cavity formation.

 

IMAGE: S. SPUTIGENA CELLS FORM A HONEYCOMB-LIKE STRUCTURE THAT ENCAPSULATES S. MUTANS TO GREATLY INCREASE AND CONCENNTRATE ACID PRODUCTION THAT BOOST CARIES DEVELOPMENT AND SEVERITY view more 

CREDIT: HYUN (MICHEL) KOO

Philadelphia — Collaborating researchers from the University of Pennsylvania School of Dental Medicine and the Adams School of Dentistry and Gillings School of Global Public Health at the University of North Carolina have discovered that a bacterial species called Selenomonas sputigena can have a major role in causing tooth decay.

Scientists have long considered another bacterial species, the plaque-forming, acid-making Streptococcus mutans, as the principal cause of tooth decay—also known as dental caries. However, in the study, which appeared 22 May in Nature Communications, the Penn Dental Medicine and UNC researchers showed that S. sputigena, previously associated only with gum disease, can work as a key partner of S. mutans, greatly enhancing its cavity-making power.

“This was an unexpected finding that gives us new insights into the development of caries, highlights potential future targets for cavity prevention, and reveals novel mechanisms of bacterial biofilm formation that may be relevant in other clinical contexts,” said study co-senior author Hyun (Michel) Koo DDS, PhD, a professor in the Department of Orthodontics and Divisions of Pediatrics and Community Oral Health and Co-Director of the Center for Innovation & Precision Dentistry at Penn Dental Medicine.

The other two co-senior authors of the study were Kimon Divaris, PhD, DDS, professor at UNC’s Adams School of Dentistry, and Di Wu, PhD, associate professor at the Adams School and at the UNC Gillings School of Global Public Health.

“This was a perfect example of collaborative science that couldn’t have been done without the complementary expertise of many groups and individual investigators and trainees,” Divaris said.

Caries is considered the most common chronic disease in children and adults in the U.S. and worldwide. It arises when S. mutans and other acid-making bacteria are insufficiently removed by teeth-brushing and other oral care methods, and end up forming a protective biofilm, or “plaque,” on teeth. Within plaque, these bacteria consume sugars from drinks or food, converting them to acids. If the plaque is left in place for too long, these acids start to erode the enamel of affected teeth, in time creating cavities.

Scientists in past studies of plaque bacterial contents have identified a variety of other species in addition to S. mutans. These include species of Selenomonas, an “anaerobic,” non oxygen-requiring group of bacteria that are more commonly found beneath the gum in cases of gum disease. But the new study is the first to identify a cavity-causing role for a specific Selenomonas species.

The UNC researchers took samples of plaque from the teeth of 300 children aged 3-5 years, half of whom had caries, and, with key assistance from Koo’s laboratory, analyzed the samples using an array of advanced tests. The tests included sequencing of bacterial gene activity in the samples, analyses of the biological pathways implied by this bacterial activity, and even direct microscopic imaging. The researchers then validated their findings on a further set of 116 plaque samples from 3 to 5-year-olds.

The data showed that although S. sputigena is only one of several caries-linked bacterial species in plaque besides S. mutans, and does not cause caries on its own, it has a striking ability to partner with S. mutans to boost the caries process.

S. mutans is known to use available sugar to build sticky constructions called glucans that are part of the protective plaque environment. The researchers observed that S. sputigena, which possesses small appendages allowing it to move across surfaces, can become trapped by these glucans. Once trapped, S. sputigena proliferates rapidly, using its own cells to make honeycomb-shaped “superstructures” that encapsulate and protect S. mutans. The result of this unexpected partnership, as the researchers showed using animal models, is a greatly increased and concentrated production of acid, which significantly worsens caries severity.

The findings, Koo said, show a more complex microbial interaction than was thought to occur, and provide a better understanding of how childhood cavities develop—an understanding that could lead to better ways of preventing cavities.

“Disrupting these protective S. sputigena superstructures using specific enzymes or more precise and effective methods of tooth-brushing could be one approach,” Koo said.

The researchers now plan to study in more detail how this anaerobic motile bacterium ends up in the aerobic environment of the tooth surface.

“This phenomenon in which a bacterium from one type of environment moves into a new environment and interacts with the bacteria living there, building these remarkable superstructures, should be of broad interest to microbiologists,” Koo said.

“Selenomonas sputigena acts as a pathobiont mediating spatial structure and biofilm virulence in early childhood caries” was co-authored by Hunyong Cho, Zhi Ren, Kimon Divaris, Jeffrey Roach, Bridget Lin, Chuwen Liu, M. Andrea Azcarate-Peril, Miguel Simancas-Pallares, Poojan Shrestha, Alena Orlenko, Jeannie Ginnis, Kari North, Andrea Ferreira Zandona, Apoena Aguiar Ribeiro, Di Wu and Hyun “Michel” Koo.

The work was funded in part by the National Institutes of Health (U01DE025046, R01DE025220, R03DE028983).

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JOURNAL

Nature Communications

DOI

10.1038/s41467-023-38346-3 

Sensory adapted dental rooms significantly reduce autistic children’s physiological and behavioral stress during teeth cleanings

Results of USC–CHLA study of 162 autistic children show that safe and feasible adaptations to the clinic environment created more relaxed, less anxious dental care experiences.

Peer-Reviewed Publication

UNIVERSITY OF SOUTHERN CALIFORNIA

 

IMAGE: IN THE SADE RESEARCH CLINIC AT CHILDREN’S HOSPITAL LOS ANGELES, SENSORY ADAPTATIONS TO THE ENVIRONMENT WERE SHOWN TO SIGNIFICANTLY REDUCE AUTISTIC CHILDREN’S PHYSIOLOGICAL AND BEHAVIORAL STRESS DURING DENTAL CLEANINGS view more 

CREDIT: PHIL CHANNING/USC

New results from a study led by USC researchers at Children’s Hospital Los Angeles show that a sensory adapted dental clinic environment creates less distressing oral care experiences for autistic children. The open-access article is available today in JAMA Network Open.

“We’ve shown that the combination of curated visual, auditory and tactile adaptations — all of which are easily implemented, relatively inexpensive and don’t require training to safely use — led to statistically significant decreases in autistic children’s behavioral and physiological distress during dental cleanings,” said lead author Leah Stein Duker, assistant professor at the USC Chan Division of Occupational Science and Occupational Therapy.

Compared to typically developing peers, autistic children experience greater oral health care challenges, which are often associated with heightened responses to sensory input. The dentist’s office is filled with potentially overwhelming stimuli such as bright fluorescent lighting, whirring electric hand tools and reclining chairs. Stein Duker and the Sensory Adapted Dental Environments (SADE) research team, including colleagues from the Ostrow School of Dentistry of USC, are identifying and testing innovative approaches that can help alleviate those challenges in order to increase access and efficacy of oral care.

In this study, autistic children received cleanings in both a standard clinic environment and an adapted one. In the adapted setting, the dentist wore a surgical loupe with attached lamp, blackout curtains were hung over the windows and a slow-motion visual effect was projected onto the ceiling (children could choose between a “Finding Nemo” underwater scene or lava lamp-style abstract colors). A portable speaker played calming nature sounds and quiet piano music. A traditional lead X-ray bib placed on the child’s chest and a “butterfly” wrap secured around the dental chair provided deep pressure hugging sensation from shoulder to ankle, which has been shown to calm the nervous system.

Electrodes placed on the child’s fingers measured electrodermal activity, a physiological correlate of sympathetic nervous system activation akin to the fight-or-flight response. The researchers also observed the frequency and duration of distressed behaviors exhibited by the child during the cleaning, such as jerking away from the dentist, clamping down with the jaw, intentionally trying to bite the dentist or keep tools out of the mouth, crying and screaming.

The researchers did not find any differences in the quality of care provided in the adapted environment, compared to the regular environment. They also did not find any significant differences in the amount of time required to get the child seated and ready for the cleaning, demonstrating that adaptations do not create logistical hurdles.

“So many interventions try to change the person” Stein Duker said. “Instead, this intervention sees children for who they are — it does not try to fix or change them — focusing the intervention to modify problematic environmental factors as a way to empower the child and family to engage successfully in occupation.”

Adaptations can make all the difference

This publication is the latest from the SADE research project, led by Principal Investigator Professor Sharon Cermak, which dates back to 2011. Since then, the SADE intervention has been replicated in pilot studies with a number of different populations in several countries. However, Stein Duker said, this study is the first with a large enough sample size to attain full statistical power.

“Because it’s a fully-powered study, we were able to identify some other very exciting findings,” Stein Duker said. “For example, our data showed that children’s physiological stress dropped as soon as they entered the adapted dental cleaning room before the actual cleaning even began, and that level of physiological stress predicted behavioral distress during the cleaning.”

The researchers also identified factors predicting the intervention’s success for any given participant: younger age and lower IQ and/or lower expressive communication level were each associated with a proportionally greater reduction in participants’ stress.

“My daughter cannot even hear the word ‘dentist,’” said one participant’s parent. “But after being in the [SADE] room for a bit, she was able to have her teeth looked at for the first time in over a year.”

In addition to oral care disparities experienced specifically by autistic children, the study may also help close an ethnic disparity gap, as 72 percent of parents of the children enrolled self-identified as Hispanic. (Note: the term “Hispanic” is used in the US to refer to people who identify as Hispanic, Latino, Chicano, Latinx, Latine, etc., which appears to be a preferred pan-ethnic term among those who expressed a preference). Data has shown that Hispanic children in the US have oral health disparities: 52 percent of Hispanic youth ages 2-19 years have dental caries (cavities), which is the highest population prevalence compared to non-Hispanic Black (44 percent), Asian (43 percent) and White (39 percent) youth. Bilingual members of the SADE research team ensured fidelity with Spanish-speaking participants and families.

Stein Duker and her Tailored Environmental Modifications lab will next study the effectiveness of a modified SADE for typically developing children with dental fear and anxiety, a major challenge in pediatric dentistry experienced by approximately 20 percent of all US children. In the near future, she is also planning to collect preliminary data studying adolescents and adults with intellectual developmental disabilities and/or autism, populations she gets frequently asked about at dental conferences and research meetings.

“Regardless of population, my advice to dental professionals and parents alike is to work together to find ways to improve the overall clinic experience,” Stein Duker says. “There are weighted X-ray bibs in every single dental office that may help calm the child; they can wear sunglasses; they can wear a beanie hat covering the ears to muffle noises — all of these are completely free and easy adaptations that have the potential to improve the clinic experience for those with sensory sensitivities, without negatively impacting dentists’ ability to provide care.”

Core technologies using generative AI in smart manufacturing of dental crowns

 

 

IMAGE: PROJECT CO-INVESTIGATOR DR HAO DING AND THE DESIGN OF A TOOTH CROWN USING GENERATIVE AI. (SMALL PHOTO) TOOTH TAILORED BY GENERATIVE AI. view more 

CREDIT: THE UNIVERSITY OF HONG KONG

Leading researchers from the Faculty of Dentistry at the University of Hong Kong (HKU) have developed a novel smart manufacturing on dental crowns by using generative artificial intelligence (AI) that leverage dental manufacturing technology.

The team, led by Dr James Tsoi, Associate Professor in Dental Materials Science collaborated with colleagues from HKU Faculty of Engineering’s Department of Computer Science to take a leap forward for the next-generation AI-designed dental prosthesis production workflow.

The researchers developed a generative AI algorithm that uses a true three-dimensional (3D) deep learning approach, producing personalised dental crowns with high accuracy that mimic the morphology and match the materials required for the biomechanics of natural teeth. Biomechanical finite element analysis revealed that by using lithium silicate, the AI-designed crown can come very close to achieving the expected lifespan of natural teeth. In contrast, the two existing methods of designing dental crowns result in crowns that are either too large or too thin, and fall short of matching the same lifespan as natural teeth.

The results have been published in leading academic journal Dental Materials in an article titled ‘Morphology and mechanical performance of dental crown designed by 3D-DCGAN’.

Currently, the Computer-Aided Design and Manufacturing (CAD/CAM) digital workflow has significantly improved dentistry but still has its challenges. From the design to the manufacture of dental prostheses, the process is labour-intensive, time-consuming, and generates health and environmental hazards during the 3D printing and milling processes. The software uses a ‘tooth library’ that contains predefined crown templates to assist in generating prosthetic designs but further adjustments are still needed by the operator to meet individual conditions.

The smart manufacturing method developed by the research team can meet the challenge and help replace the conventional approach to designing personalised dental crowns.

“We used a 3D-DCGAN (3D-Deep Convolutional Generative Adversarial Network) approach to ‘teach’ the AI algorithm ‘good’ designs by feeding the algorithm with over 600 cases of natural and healthy dentition. The algorithm improves the quality of the design through internal competition between a generator and a discriminator,” said Dr Hao Ding, a co-investigator on the project.

“During the training process, natural teeth morphological features were learned by the algorithm, so that it can design dental crowns comparable to a natural tooth — both morphologically and functionally.” Dr Ding added.

The 3D-DCGAN AI-designed crowns were compared with natural teeth and with two other conventional CAD methods of crown design methods. The results revealed that the generative AI-designed crowns had the lowest 3D discrepancy, closest cusp angle (morphological feature), and similar occlusal contacts (functional feature) as compared to natural teeth.

“This demonstrates that 3D-DCGAN could be utilised to design personalised dental crowns with high accuracy that can not only mimic both the morphology and biomechanics of natural teeth, but also operate without any additional human fine-tuning, thus saving additional costs in the production process,” said principal investigator Dr James Tsoi.

“Many AI approaches design a ‘look alike’ product, but I believe this is the first project that functionalise data-driven AI into real dental application. We hope this smart manufacturing technology will be the stepping-stone for driving Industry 4.0 in dentistry, which is vital to meet the challenges of ageing society and lack of dental personnel in Hong Kong.” He added.

Dr Tsoi said the breakthrough marks an important step towards leveraging the dental industry in Great Bay Area, which sees an annual USD3.3B revenue for producing 25-30% dental prosthesis globally, and to align with the National 14th Five-year plan in developing new forms of industrialisation and informatisation viz. smart intelligent manufacturing.

Clinical trials for using this generative AI for dental crowns are underway. The team is also working on the applicability of this tool in other dental prostheses such as bridges and dentures.

The study was supported by the General Research Fund (GRF), the Innovation and Technology Fund Mainland-Hong Kong Joint Funding Scheme (ITF-MHKJFS), and the Health and Medical Research Fund (HMRF). Its preliminary results were presented by Dr Hao Ding at the 35th Annual Scientific Meeting of the International Association of Dental Research (IADR) Southeast Asia (SEA) and it was awarded the leading IADR-SEA Research Category Award (Dental Materials and Biomaterials Category) in 2021.

The article in Dental Materials titled ‘Morphology and mechanical performance of dental crown designed by 3D-DCGAN’  published in Dental Materials, can be accessed through this link. 

Novel antibiotic-delivery system to target aggressive gum infections in adolescents

 

IMAGE: ANGELA BROWN, AN ASSOCIATE PROFESSOR OF CHEMICAL AND BIOMOLECULAR ENGINEERING IN LEHIGH UNIVERSITY’S P.C. ROSSIN COLLEGE OF ENGINEERING AND APPLIED SCIENCE, RECEIVED AN EXPLORATORY/DEVELOPMENT RESEARCH GRANT AWARD (R21) FROM THE NIH TO DEVELOP A NONSURGICAL DRUG DELIVERY SYSTEM THAT WILL ENABLE THE CONTROLLED DELIVERY OF ANTIBIOTICS TO TREAT AGGRESSIVE PERIODONTITIS IN ADOLESCENTS. view more 

CREDIT: LEHIGH UNIVERSITY

Aggressive periodontitis is a severe type of gum infection that causes the destruction of ligament and bone and can lead to tooth loss in otherwise healthy individuals. Traditional treatment typically involves deep cleaning and antibiotics. 

Lehigh University researcher Angela Brown and her team were recently awarded a grant from the National Institutes of Health (NIH) to pursue a novel treatment alternative. 

Brown, an associate professor of chemical and biomolecular engineering in Lehigh’s P.C. Rossin College of Engineering and Applied Science, received an Exploratory/Development Research Grant Award (R21) to develop a nonsurgical drug delivery system that will enable the controlled delivery of antibiotics to treat aggressive periodontitis in adolescents. According to the NIH, R21 grants are meant to encourage research in high risk/high reward areas that could lead to significant breakthroughs or yield novel techniques, methods, and applications that will benefit biomedical, behavioral, or clinical research. 

“The way these infections are typically treated is by scaling and planing, which essentially means scraping off the bacteria, and then prescribing oral antibiotics,” says Brown. “And while that tends to work, sometimes the bacteria come back, and then you have to start the course of antibiotics all over again. The more frequently you take antibiotics, the greater the chances the bacteria will become resistant to them.” 

Antibiotic resistance is indeed a growing problem. According to the Centers for Disease Control and Prevention, more than 2.8 million antimicrobial-resistant infections occur every year in the U.S., and more than 35,000 people die as a result.

In previous work, Brown and her team have shown that antibiotics can be encapsulated in liposomes—tiny, round vesicles that contain one or more membranes and can be used as a delivery mechanism. They’ve also shown that the toxin released by the periodontitis-causing bacteria, called leukotoxin, triggers the release of the antibiotics.

“Leukotoxin fights the body’s immune response by binding with cholesterol in the membrane of white blood cells, disrupting the membrane and killing the cells,” she says. “So we’re creating a liposome that has cholesterol, and we’re hoping that all or most of the toxin will bind onto the liposome instead of the host cells,” says Brown. “When the toxin binds to the liposome, it should cause a release of the antibiotics, killing the disease-causing bacteria.”

This grant will support the cell culture work her lab will perform to determine if the approach can protect the host cells from the toxin while simultaneously killing the bacterial cells. They will do this using a "co-culture" model, in which human immune cells and bacterial cells are grown together. 

The ultimate goal, she says, is to provide an alternative method of delivering antibiotics to treat aggressive periodontitis. 

“We’d also like to continue showing the advantages of using controlled delivery strategies for antibiotics,” she says. “And because this toxin we’re working with is closely related to those that cause diseases like whooping cough and cholera and E. coli infections, this approach could be useful against a range of bacteria.”

Brown has been working with leukotoxins since she was a postdoctoral student. At that time, she was focusing on how the toxin interacted with the cell membrane. Her research team found that when they encapsulated fluorescent dye inside a cell, the toxin caused the release of the dye.

“Because I’m an engineer, I had this thought, Okay, now that we know the toxin has that effect, how can we use that?” she says. “It was just a vague idea back then, but I was thinking about how cool it would be if we could encapsulate antibiotics inside cells.”

Years later, the vague idea became real. One of her master’s students, Ziang Li—now a PhD student co-advised by both Brown and Professor Steve McIntosh, who chairs Lehigh’s chemical and biomolecular engineering department—wanted to research drug delivery mechanisms.

“At the time, it wasn’t something our lab was doing, but I said to him, ‘I have this crazy idea, do you want to try it?’”

With significant support from a Lehigh Faculty Innovation Grant, Li was able to collect the preliminary data that ultimately led to the NIH funding.

“Looking at different delivery strategies for antibiotics represents a new direction for my lab,” she says. “This is our first externally funded project to do this work, and it validates the idea that this approach has a lot of potential to solve problems with both disease and with antibiotic resistance.”    

Research reported in this story is supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under award number R21DE032153.

Related Links

• Faculty Profile: Angela Brown
• NIH RePORTER (R21DE032153): "Controlled antibiotic delivery vehicle for treatment of aggressive periodontitis"

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Gum disease may lie at the root of some arthritis flare-ups

 NEWS RELEASE 17-APR-2023

Peer-Reviewed Publication

ROCKEFELLER UNIVERSITY

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IMAGE: BLOOD VESSELS IN THE SOFT TISSUE BETWEEN JOINTS, DURING A RHEUMATOID ARTHRITIS FLARE-UP. view more 

CREDIT: LABORATORY OF MOLECULAR NEURO-ONCOLOGY AT THE ROCKEFELLER UNIVERSITY

It’s a well-documented medical mystery: Patients with gum disease are less likely to respond to rheumatoid arthritis treatments. But new research may help explain this link between gum disease and an otherwise disparate condition. The findings, published in Science Translational Medicine, suggests that breaches in damaged gums allow bacteria in the mouth to seep into the bloodstream, activating an immune response that ultimately pivots to target the body’s own proteins and causes arthritis flare-ups.

“If oral bacteria are getting in and repeatedly triggering immune responses relevant to rheumatoid arthritis, that could make it harder to treat,” says Dana Orange, a professor of clinical investigation in the laboratory of Robert B. Darnell at The Rockefeller University. “When doctors encounter arthritis patients who do not respond to treatment, it would be worth it to make sure they aren’t missing an underlying gum disease, which is quite treatable.”

The Darnell lab had been following a small group of arthritis patients over the course of several years, collecting weekly blood samples and looking for changes in gene expression to help explain why painful flare-ups occur, when they noticed a surprising trend. Two of their patients, who had moderate to severe periodontal disease, had repeated episodes of oral bacteria in their bloodstreams, even when they weren’t having dental work.

Orange knew that rheumatoid arthritis patients generally have autoantibodies in their bloodstream (rheumatoid arthritis is an auto-immune disease, wherein antibodies attack the body’s own proteins and peptides). In many cases, autoantibodies take specific aim at proteins bearing the signs of citrullination, a process by which one amino acid in the protein is converted into a different one.

Upon further examination, the team discovered that the oral bacteria they detected in the blood are also citrullinated in the mouth, much like the proteins targeted by autoantibodies in arthritis. They then demonstrated that the same autoantibodies that take potshots at the body’s citrullinated proteins activate in response to citrullinated bacteria.

The results may explain why arthritis treatments do not work as well in patients with gum disease. If the gums are continuously releasing immune triggers into the bloodstream, treating arthritis without first solving the periodontal problem is like trying to haul water out of a ship without first plugging up its leaks.

“Gum disease is quite curable; rheumatoid arthritis can be much more difficult to treat,” Orange says. “Our results indicate that periodontal disease leads to leaky gums that allow oral bacteria to enter the blood repeatedly. This level of oral bacteria in blood doesn’t cause obvious symptoms, so the patients were not aware this was happening, but they do trigger inflammatory and auto-antibody responses that are highly relevant to rheumatoid arthritis.”

These findings also demonstrate the importance of conducting long-term research to better understand chronic diseases. The present study would not have been possible without a unique initiative, pioneered by Orange and Darnell several years ago, that empowers arthritis patients to collect their own blood samples at home with a finger-prick kit and mail weekly samples to Rockefeller. The lab now has several years of data to help track what happens in the blood right before an arthritis flare.

“Without having weekly blood samples for at least a year, we wouldn’t have been able to find out what was happening before the patients had symptoms of their flares,” Orange says. “Our study revealed a plausible mechanism to explain why rheumatoid arthritis patients with periodontal disease do not respond well to treatment—something very hard to capture without long-term monitoring.”

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JOURNAL

Science Translational Medicine

DOI

10.1126/scitranslmed.abq8476 

ARTICLE TITLE

Oral mucosal breaks trigger anti-citrullinated bacterial and human protein antibody responses in rheumatoid arthritis