Dental biorhythm is associated with adolescent weight gain

 

Research led by the University of Kent has discovered evidence of a biorhythm in human primary teeth that is associated with weight gain during adolescence.

 

An international research team led by Dr Patrick Mahoney at Kent’s School of Anthropology and Conservation discovered the biorhythm in primary ‘milk’ molars (Retzius periodicity [RP]) is related to aspects of physical development during early adolescence. A faster dental biorhythm produced smaller gains in weight and mass.

 

RP forms through a circadian-like process, occurring with a repeat interval that can be measured with a resolution of days. The rhythm relates to the period in which tooth enamel forms and is consistent within the permanent molars of individuals that do not retain evidence of developmental stress. The human modal RP has a near seven-day cycle but can vary from five to 12 days.

 

The first-of-its-kind research published by Nature Communications Medicine found that adolescents with a faster biorhythm (five or six-day cycle) weighed less, gained the least weight, and had the smallest change in their body mass index over a 14-month period compared to those with a slower biorhythm. Those with a slow biorhythm (seven or eight-day cycle) produced the greatest weight gain.

 

Dental histologists have known about the biological rhythm for over 100 years, but its significance for body mass and growth emerged recently in studies that compare mammalian species. Research has now focused on the meaning of the rhythm for humans.

 

One surprising finding was that participants with slower biorhythms were six times more likely to have a very high body mass index. Rapid change in body size is a natural consequence of adolescence, but excessive weight gain during puberty can have vast consequences for health such as obesity in adulthood.

 

Dr Mahoney said: ‘This research is an exciting first step. The next step is to determine if the link we have discovered extends to related adverse health outcomes for adults. Potentially, milk teeth may hold a record of this information many years before those outcomes can manifest in adults.’

 

Dr Gina McFarlane, a histologist on the project (also based at Kent), said: ‘Our findings provide a new avenue from which to explore links between overweight children and adult health risks. Milk teeth are naturally exfoliated (drop out) during the childhood years. These discarded teeth contain precise information about a fundamental growth rhythm that we now know tracks adolescent weight gain.’

 

The research paper titled ‘Dental biorhythm associates with adolescent weight gain’ is published by Nature Communications Medicine. doi: 10.1038/s43856-022-00164-x. This research project was funded by the Leverhulme Trust.

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JOURNAL

Communications Medicine

DOI

10.1038/s43856-022-00164-x 

Dentists should give antibiotics to high-risk patients to help prevent life-threatening heart infection

 

●      University of Sheffield study finds that antibiotics reduce the risk of a life-threatening heart infection following invasive dental treatment - for high-risk patients

●      Infective endocarditis (IE) is an infection of the heart valves, that causes heart failure, strokes and other serious disabilities that result in a 30 per cent, first year death rate

●      A causal link between dental treatment and IE has long been suspected with 30 to 40 per cent of cases being caused by bacteria from the mouth, however this link has been questioned due to a lack of robust research. Until now there has also never been a study to demonstrate that antibiotics are effective in reducing the risk of IE

●      Guideline committees around the world, except in the UK, recommend antibiotics are given to people at high-risk of IE before undergoing invasive dental treatment to reduce the risk of developing IE

●      University of Sheffield research is the biggest ever study to examine the link between IE and dental treatment and for the first time confirms that giving antibiotics to those at high IE-risk before invasive dental procedures, significantly reduces the risk of them developing IE

People who are at high risk of developing a life-threatening heart infection should be given antibiotics before undergoing invasive dental procedures, according to new research from the University of Sheffield.

These results suggest that current NICE guidelines, advising against routine use of antibiotics before invasive dental procedures for those at high IE-risk, should be reconsidered.

The study, led by Professor Martin Thornhill from the University’s School of Clinical Dentistry, suggests that current UK guidelines against the use of antibiotics, issued by the National Institute for Health and Care Excellence (NICE), could be putting high-risk patients at unnecessary extra risk when undergoing invasive dental procedures.

At the same time, the results validate guidance in the USA, Europe and elsewhere that recommend that those at high-risk are given antibiotics before invasive dental procedures.

Professor Martin Thornhill, Professor of Translational Research in Dentistry at the University of Sheffield and lead author of the study, said: “Infective endocarditis is a rare but devastating heart infection in which around 30 per cent of people die within the first year of developing it. We know that 30-45 per cent of IE cases are caused by bacteria that derive from the mouth, but what has been unclear and disputed until now is whether there is a strong link between invasive dental procedures, such as tooth extractions, and IE in patients who are at high risk of developing the infection.

“Results from our study validate for the first time the guidance of the major guideline committees around the world, such as The American Heart Association and the European Society for Cardiology, which recommend that those at high IE risk should receive AP before undergoing invasive dental procedures. In contrast, our data suggests that current UK NICE guidance against the routine use of AP, could be putting high risk patients at unnecessary extra risk of developing IE, and should be reviewed in light of this new evidence.”

Published in the Journal of the American College of Cardiology, the research is the biggest ever study to examine the association between infective endocarditis (IE) - a life-threatening infection of the heart often caused by bacteria that derive from the mouth - and invasive dental procedures.

The study was performed in the USA where patients at high IE-risk (those with artificial or repaired heart valves, patients with certain congenital heart conditions or a previous history of IE) are recommended to receive antibiotics before invasive dental procedures - called antibiotic prophylaxis (AP) - to reduce their risk of developing IE.

The research is the first to demonstrate that AP reduces the risk of IE following invasive dental treatment for those at high-risk of developing the infection.

Since the 1950’s, guideline committees around the world have recommended that people at increased risk of IE should be given AP before undergoing invasive dental procedures. However, there has never been any robust research directly linking dental procedures with the development of IE or any study to demonstrate that AP is effective in reducing the risk of developing IE.

Due to this lack of evidence, concerns about the unnecessary use of antibiotics and the risk that AP could promote the development of antibiotic resistant bacteria, guideline committees have since reduced the number of people that AP is recommended for - recommending that only those at high risk for IE should receive AP before invasive dental procedures. In the UK, however, NICE went even further stating that “Antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures.”

The study from Sheffield analysed the medical history of nearly eight million people in the USA over a 16 month period, including 36,773 individuals at high-risk of IE. The researchers looked at whether the patients had invasive dental treatment, if they then went on to develop IE within 30 days and whether they had been given AP before the procedure.

Researchers found that 3,774 of those studied developed IE within 30 days of dental treatment. They also found that the risk of developing IE was 160 times greater in those at high IE-risk than in the general low-risk population.

The association between invasive dental procedures an IE was particularly strong for dental extractions and oral surgical procedures. For patients at high IE-risk, the risk of developing IE was one in every 250 extractions and one in every 100 oral surgery procedures without AP cover. The risk in the general low risk population was extremely small.

The study found however, that only 32.6 per cent of high IE-risk patients received AP before invasive dental procedures. This allowed the researchers to study the effectiveness of AP. They found that the risk of developing IE was nearly 10 times greater when dental extractions were performed in high-risk patients without AP cover than when performed with AP cover. Similarly, the risk of IE was 12.5 times greater when oral surgery procedures were performed in high-risk patients without AP cover than when performed with AP cover.

For the USA, even though the study’s results validate The American Heart Association guidance, the research found that compliance with this advice was low –only 32.6 per cent of those at high risk of IE were given AP before undergoing invasive dental procedures.

Professor Thornhill added: “It is reassuring for patients, cardiologists and dentists that our data validates the American, European and other guidelines from around the world that recommend that patients at high risk for IE should receive AP before invasive dental procedures. It is concerning, however, that compliance with this guidance by dentists in the USA was so low. Clearly, more needs to be done to improve compliance with the American Heart Association guidelines.”

The study, Antibiotic Prophylaxis Against Infective Endocarditis Before Invasive Dental Procedures, is published in the Journal of the American College of Cardiology. It was performed in the United States using data from IBM Health and was funded by Delta Dental of Michigan and Renaissance Health Service Corporation in the US. To access the paper, visit: https://doi.org/10.1016/j.jacc.2022.06.030 

Applying microrobotics in endodontic treatment, diagnostics

 

 

IMAGE: MAGNETICALLY ACTUATED 3D MOLDED ROBOTS ARE CONTROLLED PRECISELY TO TARGET THE APICAL REGION OF THE ROOT CANAL UNINTERRUPTED BY THE SURROUNDING PERIODONTIUM AS VISUALIZED AND TRACKED BY CBCT. view more 

CREDIT: PENN DENTAL MEDICINE

With its irregularities and anatomical complexities, the root canal system is one of the most clinically challenging spaces in the oral cavity. As a result, biofilm not fully cleared from the nooks and crannies of the canals remains a leading cause of treatment failure and persistent endodontic infections, and there are limited means to diagnose or assess the efficacy of disinfection. One day, clinicians may have a new tool to overcome these challenges in the form of microrobots.

In a proof-of-concept study, researchers from Penn Dental Medicine and its Center for Innovation & Precision Dentistry (CiPD), have shown that microrobots can access the difficult to reach surfaces of the root canal with controlled precision, treating and disrupting biofilms and even retrieving samples for diagnostics, enabling a more personalized treatment plan. The Penn team shared their findings on the use of two different microrobotic platforms for endodontic therapy in the August issue of the Journal of Dental Research ; the work was selected for the issue’s cover.

“The technology could enable multimodal functionalities to achieve controlled, precision targeting of biofilms in hard-to-reach spaces, obtain microbiological samples, and perform targeted drug delivery, ” says Dr. Alaa Babeer, lead author of the study and a Penn Dental Medicine Doctor of Science in Dentistry (DScD) and endodontics graduate, who is now within the lab of Dr. Michel Koo, co-director of the CiPD .

In both platforms, the building blocks for the microrobots are iron oxide nanoparticles (NPs) that have both catalytic and magnetic activity and have been FDA approved for other uses.  In the first platform, a magnetic field is used to concentrate the NPs in aggregated microswarms and magnetically control them to the apical area of the tooth to disrupt and retrieve biofilms through a catalytic reaction. The second platform uses 3D printing to create miniaturized helix-shaped robots embedded with iron oxide NPs. These helicoids are guided by magnetic fields to move within the root canal, transporting bioactives or drugs that can be released on site.

“This technology offers the potential to advance clinical care on a variety of levels,” says Dr. Koo, co-corresponding author of the study with Dr. Edward Steager, a senior research investigator in Penn’s School of Engineering and Applied Science.

“One important aspect is the ability to have diagnostic as well as therapeutic applications. In the microswarm platform, we can not only remove the biofilm, but also retrieve it, enabling us identify what microorganisms caused the infection. In addition, the ability to conform to the narrow and difficult-to-reach spaces within the root canal allows for a more effective disinfection in comparison to the files and instrumentation techniques presently used.”

A Collaborative System

This microrobotics system is the outgrowth of collaborative work that has been ongoing for several years between Penn Dental Medicine and Penn Engineering. In a recent separate study, Dr. Koo and colleagues constructed the platform to electromagnetically control the microrobots, in that case, enabling microswarms of the iron oxide NPs to adopt different configurations and release antimicrobials on site to effectively treat and remove plaque from teeth.

“We see potential applications of microrobotics systems for both at-home oral care as well as in the dental office for more precise and effective tools for clinicians,” says Dr. Koo.

To determine the effectiveness of the endodontic microrobotic systems to disrupt and retrieve biofilm from the root canal, the researchers conducted experiments in vertically placed 3D printed tooth replicas in collaboration with Dr. Bekir Karabucak, Chair of Penn Dental Medicine’s Department of Endodontics. A mixed-species biofilm containing endodontic bacteria (Streptococcus gordonii, Enterococcus faecalis, Fusobacterium nucleatum, and Actinomyces israelii ) was prepared inside the teeth replicas and the NP suspension was introduced to the root canal. Using electromagnets, microswarms of NPs were created and precisely controlled to disrupt the biofilm. Upon analysis of the collected biofilm, they found all four species were detected, and using a microscope, all nanoparticles appeared to be removed from the root canal.

Breaking the Mold

The second system tested exploits the flexibility of iron oxide NPs as building blocks and involves creating a molded robotic system. Soft corkscrew-like molds in the form of a helicoid (two helices wrapped around a central axis) were 3D printed and filled with a NP-embedded gel. Using a magnetic field, the helicoids were shown to move through the canal with high efficiency to achieve chemical and mechanical disruption of biofilm. Of particular note is the added ability to load the helicoids with therapeutics for targeted drug delivery at the apical region of the root canal where the infection is in close proximity to the surrounding tissues.

In addition, the research team showed the unique ability of track the microrobots in real-time using existing imaging technologies such as intraoral scanner, dental x-ray, and cone-beam computed tomography that were capable of locating the helicoids in the intact tooth canal.

“Importantly, we demonstrated in an ex vivo model that the robots could be controlled by the magnetic field without interruption by the soft and hard tissue surrounding the teeth. In addition, they showed tremendous maneuverability from the top to bottom of the canal,” notes Dr. Karabucak, who explains the magnetic field for both of the endodontic systems tested would be generated by a small device in the oral cavity.

Broad Applications

Along with the potential to enhance endodontic treatment and tissue regeneration, the researchers see this technology as something that could have broad applications across medicine and industry.

“From disinfecting medical devices like catheters to ensuring clean water lines, this technology holds the potential to transform areas far beyond dental medicine,” adds Dr. Koo. “It could disrupt current modalities across disciplines.”

 

Alaa Babeer is a recent graduate of Penn Dental Medicine’s combined Endodontic residency and DScD program.

Michel Koo is a professor in the Department of Orthodontics and divisions of Community Oral Health and Pediatric Dentistry in Penn Dental Medicine and co-director of the Center for Innovation & Precision Dentistry.

Edward Steager is a senior research investigator in Penn’s School of Engineering and Applied Science.

Bekir Karabucak is chair and professor of Endodontics, director of postdoctoral Endodontics program and director of division of Advanced Dental Education at Penn Dental Medicine.

Additional coauthors on the paper are Penn Dental Medicine’s Min Jun Oh, Zhi Ren, Yuan Liu, Fernando Marques and Bekir Karabucak and State University of Rio de Janeiro School of Dentistry’s Ane Poly.

This work was supported in part by the National Institute for Dental and Craniofacial Research (grants R01 DE025848 and R56 DE029985), the National Research Foundation of Korea funded by the Ministry of Education (No. NRF-2021R1A6A3A03044553), Colgate-Palmolive Fellowship, and the NIDCR Postdoctoral Training Program under award number R90DE031532.

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JOURNAL

Journal of Dental Research

DOI

10.1177/00220345221087149

Ditching the toothbrush for whiter teeth, fewer cavities (video)

 

AMERICAN CHEMICAL SOCIETY

 

IMAGE: A NEW HYDROGEL TREATMENT BREAKS APART CAVITY-FORMING BIOFILMS AND WHITENS TEETH WITHOUT DAMAGING ENAMEL. view more 

CREDIT: AMERICAN CHEMICAL SOCIETY

The first thing people notice when they meet you is your smile. To be more confident when giving wide-mouthed, eye-crinkling smiles, people want healthy, pearly white teeth. But toothpastes only remove surface stains, and whitening treatments can harm enamel, leading to cavities and discoloration. Now, researchers in ACS Applied Materials & Interfaces report a new hydrogel treatment that breaks apart cavity-forming biofilms and whitens teeth without damaging them. Watch a video of the treatment here.

Daily toothbrushing and flossing are good ways to prevent cavities from forming, according to the American Dental Association. However, these methods don’t effectively whiten teeth. For better whitening, consumers often turn to over-the-counter or professional treatments that combine hydrogen peroxide-containing gels and blue light, producing a chemical reaction that removes stains. This combination removes most of the discoloration, but generates reactive oxygen species that can break down enamel. Previously, Xiaolei Wang, Lan Liao and colleagues modified titanium dioxide nanoparticles for a less destructive tooth-whitening treatment. This method still required high-intensity blue light, which can damage nearby skin and eyes. So, the team wanted to find a material that would be activated by green light — a safer alternative — to both whiten teeth and prevent cavities.

The researchers combined bismuth oxychloride nanoparticles, copper oxide nanoparticles and sodium alginate into a thick mixture. Then, they evenly coated the mixture onto the surface of teeth stuck to a slide and sprayed the concoction with a calcium chloride solution, forming a strongly adhering hydrogel. Next, the team tested the material on teeth that were stained with coffee, tea, blueberry juice and soy sauce and placed in a lab dish. Following treatment with the hydrogel and green light, the teeth got brighter over time, and there was no damage to the enamel. In another set of experiments, the team showed that the treatment killed 94% of bacteria in biofilms. To demonstrate that the treatment could work on teeth in vivo, the team used the new method on mice whose mouths were inoculated with cavity-forming bacteria. The green-light activated hydrogel effectively prevented moderate and deep cavities from forming on the surface of the animals’ teeth. The researchers say their safe, brush-free treatment both effectively prevents cavities and whitens teeth.

The authors acknowledge funding from the National Natural Science Foundation of China, Key Youth Project of Jiangxi Province, Key Research and Development Program of Jiangxi Province, Natural Science Foundation of Jiangxi Province and the Graduate Innovation Special Fund Project of Jiangxi Province.

For more of the latest research news, register for our upcoming meeting, ACS Fall 2022. Journalists and public information officers are encouraged to apply for complimentary press registration by completing this form.

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.

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JOURNAL

ACS Applied Materials & Interfaces

DOI

10.1021/acsami.2c00887 

Dentists and dental hygienists on early front lines of COVID-19 report symptoms of anxiety, depression

The first known U.S. study to evaluate the mental health of frontline dentists and dental hygienists during the pandemic found that dental health care workers report anxiety and depression symptoms during peaks of transmission among the public.

Published jointly in the August issues of The Journal of the American Dental Association and the Journal of Dental Hygiene and available online at JADA.ada.org, the study indicates between June 2020 and June 2021, 17.7% of dental health care workers reported anxiety symptoms, 10.7% reported depression symptoms, and 8.3% reported symptoms of both. The one-year study conducted from June 2020 to June 2021, included 8,902 dental health care workers participating monthly in an anonymous longitudinal, web-based survey.

According to the findings, between June 2020 and June 2021, dental hygienists reported higher rates of depression symptoms than dentists at each surveyed time point, with depression symptom rates peaking in December 2020. Dental hygienists’ depression rates declined in 2021 as dentists’ rates of depression symptoms remained steady. At the end of the study period, both groups had relatively similar rates — 11.8% for dentists and 12.4% for hygienists.

“Interestingly, dental health care workers reported lower rates of anxiety and depression symptoms than the general public, despite being on the front lines and providing oral health care during the pandemic,” says author Stacey Dershewitz, J.D., Psy.D., Adjunct Professor of Clinical Psychology and Director of the Center Clinic at the George Washington University Professional Psychology Program. “As the pandemic continues, it is critically important that dental health care workers continue to develop their ability to recognize and address signs and symptoms of mental health conditions within themselves and their colleagues, promote healthy work environments, reduce the impact of stress on the profession, and make supports accessible to those who are struggling emotionally.”

Some participants’ anxiety symptoms decreased after receiving the COVID-19 vaccine. The study — also the first to examine the association between the COVID-19 vaccine and mental health — found that unvaccinated dental health care workers who intended to be vaccinated suffered significantly more anxiety symptoms (20.6%) compared to fully-vaccinated dental health care workers (14.1%). 

“The hope is that this is just the first of many steps in monitoring mental wellness of the entire oral care team,” says JoAnn Gurenlian, R.D.H, M.S., Ph.D, A.F.A.A.O.M., Director of Education and Research, American Dental Hygienists’ Association. “There is much work to be done to dismantle barriers to treatment and prioritize wellbeing in the oral care setting, as well as look at future research around contributing factors to mental illness that may be unique to these professions.”

The study is part of ongoing collaborative research efforts between the American Dental Association (ADA) and the American Dental Hygienists’ Associations (ADHA) to understand COVID-19’s impact on dental health care workers.

“As members of the dental profession, we are committed to improving the oral health of our patients and communities. Furthermore, as healthcare professionals, we must be committed to our own health and wellness to optimally care for others,” says study author Maria L. Geisinger, D.D.S, M.S., Professor and Director of the Advanced Education Program in Periodontology at the University of Alabama at Birmingham School of Dentistry. “Creating professional environments that allow for open communication about mental health among members of the dental team can reduce the stigma around mental health diagnoses and treatment for dental health care workers.”

AI technology to automate the process of denture design and enhance treatment efficiency without compromising accuracy

 

Loss of permanent teeth is usually caused by dental diseases or trauma and is common in the global population, especially among the elderly due to aging and relatively poorer oral health.

Failure to replace a missing tooth not only affects facial aesthetic and chewing function, but it may also lead to jawbone loss and shifting to teeth, which may cause malocclusion and bite irregularities that could have a significant impact on the health of the remaining teeth, gums, jaw muscles and jaw points.

Artificial teeth, also known as bridges and dentures, are prosthetic devices used to replace missing teeth. It is essential for the false teeth to resemble the patient’s original tooth so that the patient can retain his or her original appearance, chewing function, oral and physical health.

Currently, the process of designing and creating dentures is highly time-consuming as the existing computerised design process requires tedious manual inputs, teeth occlusion information collection as well as multiple denture fitting procedures due to limited accuracy of exciting technologies.

Researchers from the Faculty of Dentistry at the University of Hong Kong (HKU) and the Department of Computer Science of Chu Hai College of Higher Education, collaborated to develop a new approach using artificial intelligence to automate the design of individualised dentures, in order to enhance the treatment efficiency and improve patient experience.

The AI technology used in the process was based on 3D Generative Adversarial Network (3D-GAN) algorithm and tested on 175 participants recruited at HKU. The study shows that AI technology could reconstruct the shape of a natural healthy tooth and automate the process of false teeth design with high accuracy.

“The 3D GAN algorithm was selected due to its superior performance on 3D object reconstruction compared to other AI algorithms. In the preliminary study, 3D GAN was able to rebuild similar shapes to the original teeth for 60% of the cases. It is expected to mature with more AI training data,” co-Investigator, Dr Reinhard Chau explained.

The new approach only requires the digital model of a patient’s dentition to function. It can learn the features of an individual’s teeth from the rest of the dentition and generate a false tooth that looks like the missing tooth.

“This will facilitate the treatment workflow for dentists in replacing a missing tooth, as the preparation and fitting process will require minimal time, and a patient will not need to stay at the clinic for long hours,” said Principal Investigator Dr Walter Lam.

The study entitled “Artificial intelligence-designed single molar dental prostheses: A protocol of prospective experimental study” is published in the journal PLoS ONE. The preliminary results of the study were presented in the recent International Association of Dental Research (IADR) General Session. The study won the IADR Neal Garrett Clinical Research Prize and First runner-up in the 2022 IADR-SEA Hatton Award - Senior Category.

The research team members
HKU Faculty of Dentistry
Principal Investigator: Dr Walter Lam, Clinical Assistant Professor in Prosthodontics and Founding Member of HKU Musketeers Foundation Institute of Data Science
Co-investigators:
- Dr Reinhard Chau, Research Assistant in Restorative Dental Sciences and Applied Oral Sciences & Community Dental Care
- Professor Colman McGrath, Clinical Professor in Dental Public Health
- Dr Khaing Myat Thu, Senior Research Assistant in Restorative Dental Sciences

Chu Hai College of Higher Education
Co-investigator:
Professor Richard Hsung, Associate Professor in Department of Computer Science

The Journal “Artificial intelligence-designed single molar dental prostheses: A protocol of prospective experimental study”:
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0268535

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JOURNAL

PLoS ONE

DOI

10.1371/journal.pone.0268535 

Studying the link between gum disease and Alzheimer’s disease

 

Fusobacterium nucleatum (F. nucleatum) is a common type of bacteria that proliferates in periodontal disease. It affects the gums and jawbone, and if untreated results in unstable teeth and tooth loss. In recent years, F. nucleatum has been linked to conditions ranging from colorectal cancer to premature delivery of babies.

Now new research published in the journal Frontiers in Aging Neuroscience by Tufts University scientists and colleagues suggests a link between F. nucleatum and Alzheimer's disease.

"In this study, our lab is the first to find that Fusobacterium nucleatum can generate systemic inflammation and even infiltrate nervous system tissues and exacerbate the signs and symptoms of Alzheimer's disease," says Jake Jinkun Chen, professor of periodontology and director of the Division of Oral Biology at Tufts University School of Dental Medicine. The first author of the paper is Hongle Wu, who was a postdoctoral fellow in the Chen Lab at the time of the study.

F. nucleatum can also generate severe generalized inflammation, which is a symptom of many chronic diseases including Type 2 diabetes and Alzheimer's disease, notes Chen, who is also a trained pathologist and professor in the Department of Developmental, Molecular and Chemical Biology at the School of Medicine and Graduate School of Biomedical Sciences.

Chen and his colleagues believe that by targeting F. nucleatum, they can slow the spread and progression of at least two epidemics—periodontal disease, which affects 47% of U.S. adults over age 30, and Alzheimer's, which afflicts 6.5 million Americans currently, and is expected to increase to over 14 million by 2060.

F. nucleatum and Immune Cells in the Brain

The latest research, done in mice, shows that F. nucleatum results in an abnormal proliferation of microglial cells, which are immune cells in the brain that normally remove damaged neurons and infections and help maintain the overall health of the central nervous system. This over-supply of microglial cells also created an increased inflammatory response, the researchers found. Chronic inflammation or infection is believed to be a key determinant in the cognitive decline that occurs as Alzheimer's disease progresses.

"Our studies show that F. nucleatum can reduce the memory and thinking skills in mice through certain signal pathways. This is a warning sign to researchers and clinicians alike," Chen says.

Possible links between periodontal disease and Alzheimer’s have been posited by scientists in the past. While the new research does not show that F. nucleatum-related periodontal disease leads directly to Alzheimer’s disease, the new study suggests that periodontal disease caused by F. nucleatum and left untreated or poorly treated could exacerbate symptoms of Alzheimer's disease, Chen believes. Conversely, treating periodontal disease effectively in those who have early-stage Alzheimer's could potentially slow Alzheimer's progression.

"Testing for bacterial load and degree of symptoms could one day become a way to measure the effects of F. nucleatum and manage treatment to slow progression of both periodontal disease and Alzheimer's," Chen says.

Their research also suggests potential drug targets that could specifically quench the local as well as systemic inflammation caused by F. nucleatum in a periodontal environment.

Oral Infections and Systemic Diseases

More broadly, Chen and colleagues are targeting their translational research at blocking the pathways between periodontal disease and not only Alzheimer’s, but other diseases linked to inflammation, including Type 2 diabetes.

Only 2% of mRNA is translated into proteins. Ninety-eight percent of RNA is "noncoding" and traditionally has been considered as no more than "junk genes." But increasingly scientists, including Chen, are uncovering important functions they possess.

In particular, his lab is focused on two noncoding RNAs. One—microRNA—regulates the production of proteins in cells. Another—lncRNA—performs other functions to regulate gene expression and could ultimately be used to treat atherosclerosis (hardening of the arteries) as well as periodontal disease, diabetes, cancer, and diabetic bone disease.

Studies by Chen's lab have shown that a molecule called microRNA-335-5P can inhibit damage done by periodontal pathogens. The molecule could also have a robust effect in targeting the pathological molecules produced in the brain that lead to Alzheimer's.

"MicroRNA in general suppresses gene expression and could stop the production of certain proteins. MicroRNA-335-5P in particular could target three 'bad' genes—DKK1, TLR-4, and PSEN-1—all believed to be related to Alzheimer's disease," he says.

His lab has also designed a small molecule called adipoAI, which has strong anti-inflammatory properties. Chen hopes to begin a clinical trial soon to study whether it is effective in treating a range of inflammatory diseases including Type 2 diabetes, Alzheimer's disease, and periodontal disease.

"Your mouth truly is the gateway to your body," he says

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