Early childhood exposure to fluoride does not have effects on cognitive neurodevelopment.

  The International Association for Dental, Oral, and Craniofacial Research (IADR) and the American Association for Dental, Oral, and Craniofacial Research (AADOCR) have announced the publication of a new study in Journal of Dental Research that examines how cognitive development among young children is affected by early exposure to fluoride.

It is important to maintain confidence in the risk and benefit balance of major caries-preventive programs using fluoride. The ongoing debate about potential effects of early life exposures to fluoride on cognitive neurodevelopment requires high quality scientific evidence. The new study by Loc Do, The University of Queensland Faculty of Health and Behavioural Sciences, School of Dentistry, Brisbane, Australia, et al. aimed to investigate potential effects of fluoride exposure on cognitive neurodevelopment assessed with the Wechsler Adult Intelligence Scale 4th edition (WAIS-IV) in an Australian population-based sample.

“The fluoridation of drinking water has been enormously beneficial to oral health over the decades, and to public health more generally,” said AADOCR President Effie Ioannidou. “It is crucial that a wealth of scientific evidence always be available should the public ever need reminding of this fact.”

The sample was selected from the National Child Oral Health Study (NCOHS) 2012-14. NCOHS collected data on socioeconomic factors, oral health behaviors, and residential history to estimate percent lifetime exposure to fluoridated water during the first five years of life (%LEFW). NCOHS children were also examined by trained and calibrated examiners to assess dental fluorosis (a reliable and valid individual biomarker of total fluoride intake during early childhood). The sample was followed up in 2022-23 to collect data on cognitive neurodevelopment (intelligence quotient (IQ)) using the WAIS-IV, which was administered by trained and calibrated qualified psychologists.

Multivariable regression models were generated to investigate associations between the two exposure measurements (%LEFW and dental fluorosis) with full-scale IQ (FSIQ) scores, controlling for important confounding effects. Hypotheses of noninferiority were also tested contrasting different levels of exposure to fluoride. Some 357 participants aged 16-26 years completed WAIS-IV, with a mean FSIQ score of 109.2 (95%CI: 107.8-110.5). The multivariable regression models’ estimates demonstrated slightly higher the FSIQ scores among the exposed than the non-exposed. Adjusted β of 100%LEFW vs. 0%LEFW was 1.07 (95%CI: -2.86, 5.01), and of having dental fluorosis vs. no fluorosis was 0.28 (95%CI: -3.00, 3.57).

The hypothesis of non-inferiority tests found that the FSIQ scores of those exposed and non-exposed to fluoride were equivalent. The study provided consistent evidence that early childhood exposure to fluoride does not have effects on cognitive neurodevelopment.

Chewing xylitol gum linked to decrease in preterm birth

 

Study participants in the group which chewed gum with xylitol twice a day saw a 24% drop in preterm births and a 30% drop in low-birthweight babies, 

Peer-Reviewed Publication

University of Washington School of Medicine/UW Medicine

Could the incidence of preterm births be lowered by … chewing gum?

New research suggests “yes.”

Results from a study in Malawi showed that chewing gum containing xylitol, a naturally occurring alcohol sugar, was associated with a 24% reduction in preterm birth. The findings were published today in Med (a Cell Press journal).

Researchers found that the group of pregnant individuals randomized to receive chewing gum also saw a 30% drop in low-birthweight babies, when compared with the control group which did not receive xylitol gum, noted lead author Dr. Greg Valentine, associate professor of pediatrics at the University of Washington School of Medicine. 

“It surprised us all that such a simple intervention could have such a dramatic effect,” said Valentine. 

The study followed two randomly selected groups of patients over three years in Malawi with over 10,000 participants, noted senior author Dr. Kjersti Aagaard, medical director of HCA Healthcare, who started the study at Baylor College of Medicine. 

A total of 4,549 patient participants received the xylitol chewing gum intervention while 5,520 the control group received traditional counseling and medication. The study was conducted from May 2015 to October 2018. The data analysis and follow-up was completed in October 2021.

Previous research has shown that, during pregnancy, periodontal disease (also known as gum disease) is associated with a two- to threefold increase in risk for preterm birth and low-birthweight delivery. 

While little evidence exists to identify the mechanism behind this link, it might be explained by the inflammatory response associated with periodontal disease, or through the spread of bacteria from the mouth through the bloodstream to organs throughout the body, the researchers surmised. 

In humans, 1 mm of dental plaque contains 100 million bacteria, including pathogens. These bacteria can cause infection and inflammation throughout the body, the report stated. 

Xylitol is a naturally occurring sugar alcohol sweetener used in chewing gum, lozenges and candies that have probiotic properties. Studies have shown that xylitol can both reduce the growth of bacteria strongly associated with periodontal disease and independently reduce inflammation in gum tissues, researchers noted.  

In the Prevention of Prematurity and Xylitol trial, participants were enrolled before they became pregnant and in early pregnancy (before 20 weeks gestation) and followed until birth. Trying to treat periodontal disease via traditional methods, such as deep cleaning to remove plaque under the gum tissue, and encouraging the use of toothbrushes and toothpaste, is difficult in low-resource countries due to lack of supplies, shortages of healthcare workers, and the lack of clean running water, Valentine said. 

A simple intervention like chewing gum helps overcome those issues by improving oral health in a more accessible manner, he said.

The individuals enrolled in the trial in eight Malawi health centers chewed xylitol-containing gum from early pregnancy until delivery.

“Basically, we know that periodontal disease is associated with preterm birth,” Valentine said.  “This is particularly significant in Malawi, since about 70% of the pregnant individuals suffer from gum disease.”

Malawi has one of the highest incidences of preterm birth worldwide, with preterm birth occurring in up to 20% of births, the researchers noted. Preterm birth is the leading cause of death worldwide for children under 5, the report noted. 

Valentine is leading another Malawi trial, the Prevention of Developmental Delay and Xylitol study. It follows 1,000 children born during the initial trial to study neurodevelopmental outcomes between 4 and 8 years of age. 

That study seeks to evaluate whether xylitol in pregnancy affects the children’s development, growth, hearing and vision. The study is important to ensure no long-term harm occurred to children exposed to xylitol, Valentine said. Those results are expected in 2027.

The researchers plan to test the xylitol-gum intervention in pregnancies in lower-resourced communities in the Seattle area, he added. 

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Journal

Med

DOI

10.1016/j.medj.2024.10.016 

The worldwide economic effects of oral health conditions

 

Peer-Reviewed Publication

International Association for Dental, Oral, and Craniofacial Research

Alexandria, VA – The International Association for Dental, Oral, and Craniofacial Research (IADR) and the American Association for Dental, Oral, and Craniofacial Research (AADOCR) have announced the publication of a study in Journal of Dental Research that examines the overall effects of oral health on global, regional, and national economies.

The recent WHO Oral Health Resolution and the subsequent WHO Global Oral Health Action Plan highlight the key relevance of providing information on the economic impacts of oral conditions. The purpose of this study was to provide updated estimates for the global, regional and country-level economic impacts of oral conditions in 2019. Extending previously established methods, dental expenditures (costs for treatments) and productivity losses for five oral conditions (caries in deciduous & permanent teeth, periodontitis, edentulism, other oral diseases) were estimated for the year 2019.

“These findings demonstrate the enormous global economic burden that arises from oral diseases due to the costs of treatment and losses in productivity,” said JDR Editor-in-Chief Nick Jakubovics. “Oral diseases must be included in the upcoming United Nations High-Level Meetings on Non-Communicable Diseases and Universal Health Coverage.”

The estimated total worldwide economic impacts of dental diseases in 2019 were $710B, whereof $387B ($327B-$404B) due to direct costs and $323B ($186B-$460B) due to productivity losses for the five main oral conditions. Low Income countries spent an average of $0.52 ($0.22-$0.96) per capita on dental care, while High Income countries spent an average of $260 ($257-$268) per capita – a 500-fold difference. These findings suggest that the prevention and treatment of oral diseases continue to substantiate an enormous economic burden to individuals and society.

The comprehensiveness of estimates supersedes that of previous work as the primary information on direct costs was identified for a higher number of countries. The need for more and better routine reporting and monitoring of the economic impact of oral conditions is emphasized, particularly for the WHO Eastern Mediterranean and African regions. The relevance of such information is also highlighted by its inclusion in the first-ever WHO Global Oral Health Status Report and Global Strategy on Oral health 2023-2030. Given the persistently high economic burden of oral conditions, there is a key role for better prioritization of cost-efficient oral health programs as well as needs-responsive capacity planning.

Bacteria involved in gum disease linked to increased risk of head and neck cancer

 

More than a dozen bacterial species among the hundreds that live in people’s mouths have been linked to a collective 50% increased chance of developing head and neck squamous cell carcinoma (HNSCC), a new study shows. Some of these microbes had previously been shown to contribute to periodontal disease, serious gum infections that can eat away at the jawbone and the soft tissues that surround teeth.

Experts have long observed that those with poor oral health are statistically more vulnerable than those with healthier mouths to HNSCC, a group that includes the most common cancers of the mouth and throat. While small studies have tied some bacteria in these regions (the oral microbiome) to the cancers, the exact bacterial types most involved had until now remained unclear.

Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, the new analyses looked at the genetic makeup of oral microbes collected from healthy men and women. Of the hundreds of different bacteria that are routinely found in the mouth, 13 species were shown to either raise or lower risk of HNSCC. Overall, this group was linked to a 30% greater likelihood of developing the cancers. In combination with five other species that are often seen in gum disease, the overall risk was increased by 50%.

“Our findings offer new insight into the relationship between the oral microbiome and head and neck cancers,” said study lead author Soyoung Kwak, PhD. “These bacteria may serve as biomarkers for experts to flag those at high risk,” added Kwak, a postdoctoral fellow in the Department of Population Health at NYU Grossman School of Medicine.

Previous investigations had uncovered certain bacteria in tumor samples of people already diagnosed with these cancers, says Kwak. Then, in a small 2018 assessment, the current research team explored how microbes in healthy participants may over time contribute to future risk of HNSCC.

Their latest report, publishing online Sept. 26 in the journal JAMA Oncology, is the largest and most detailed analysis of its kind to date, says Kwak. It is also among the first to examine whether common fungi, organisms like yeast and mold that, along with bacteria, make up the oral microbiome, might play a role in HNSCC. The new experiments found no such role for fungal organisms.

For the research, the team analyzed data from three ongoing investigations tracking 159,840 Americans from across the country to better understand how diet, lifestyle, medical history, and many other factors are involved in cancer. The data were gathered for the American Cancer Society Cancer Prevention Study II; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; and the Southern Community Cohort Study.

Shortly after enrolling, participants rinsed with mouthwash, providing saliva samples that preserved the numbers and species of microbes for testing. Researchers then followed up for roughly 10 to 15 years to record any presence of tumors.

In the current study, the investigators analyzed bacterial and fungal DNA from the spit samples. Then, they identified 236 patients who were diagnosed with HNSCC and compared the DNA of their oral microbes with that of 458 randomly selected study subjects who had remained cancer-free. In their research, the team accounted for factors known to play a role, such as age, race, and how often they smoked cigarettes or drank alcohol.

“Our results offer yet another reason to keep up good oral-hygiene habits,” said study co-senior author Richard Hayes, DDS, MPH, PhD. “Brushing your teeth and flossing may not only help prevent periodontal disease, but also may protect against head and neck cancer,” added Hayes, a professor in the Department of Population Health at NYU Grossman School of Medicine and a member of its Perlmutter Cancer Center.

The researchers emphasized that their study was designed to identify correlations between risk of cancer and certain bacteria in the mouth, but not to establish a direct cause-and-effect link. That will require further research.

“Now that we have identified key bacteria that may contribute to this disease, we next plan to explore the mechanisms that allow them to do so and in what ways we can best intervene,” said study co-senior author Jiyoung Ahn, PhD. Ahn is a professor in the Departments of Population Health and Medicine at NYU Grossman School of Medicine and is the associate director for population research at its Perlmutter Cancer Center.

Ahn cautions that while the added risks from bacteria are concerning, overall cases of head and neck cancer remain fairly uncommon.

Intensive diabetes treatment reduces gum disease inflammation

A research group at Osaka University revealed that intensive treatment for diabetes can improve the inflammatory state of periodontal disease.

Peer-Reviewed Publication

Osaka University

 

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Improving periodontal inflammation by glycemic control treatment

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Credit: Moe Inoue

Osaka, Japan – While the link between diabetes and periodontal disease is known, the impact of diabetes treatment on periodontal health is less well understood. Recent research published in Diabetes, Obesity and Metabolism demonstrates that periodontal inflammation can be positively affected just by receiving intensive diabetes treatment.

It is widely believed that there is an interrelationship between diabetes and periodontal disease. While it has been shown that treatment of periodontal disease improves blood glucose control, the effect of diabetes treatment on periodontal disease has remained largely unknown.

A collaborative research team between the Graduate Schools of Dentistry, Medicine, and Engineering at Osaka University administered a two-week intensive diabetes treatment to 29 type 2 diabetes patients, analyzing systemic, and dental indicators before and after treatment. No dental interventions were performed as part of this study; patients only received diabetes treatment. Results showed improvements in both glycoalbumin, a marker of blood sugar control, and PISA (Periodontal Inflamed Surface Area), indicating reduced blood glucose level and periodontal inflammation. Further, comparison of subjects based on PISA improvement revealed that those with significant improvement had higher pre-treatment C-peptide levels, suggesting better insulin secretion and better CVRR and ABI values, indicating less severe diabetic neuropathy and peripheral vascular disorders.

"These research findings are expected to advance our understanding of the mechanisms underlying the relationship between diabetes and periodontal disease," says senior author Masae Kuboniwa. "This study demonstrates that improving periodontal disease in diabetic patients requires not only periodontal treatment but also early diabetes management. We anticipate that promoting collaboration between medical and dental care from the early stages of diabetes can significantly contribute to preventing the onset and progression of periodontal disease in diabetic patients."

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The article, “Periodontal Tissue Susceptibility to Glycaemic Control in Type 2 Diabetes,” was published in at Diabetes, Obesity and Metabolism at DOI: http://doi.org/10.1111/dom.15835

Individuals with complications of diabetes are at higher risk of gum disease

Gum disease is more common in individuals with microvascular complications of diabetes, new research being presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Madrid, Spain (9-13 September) and published in The Journal of Dental Research has found.

Periodontitis is a chronic inflammatory disease that affects the gums and the bones supporting the teeth. It is caused by the accumulation of bacterial plaque, and if left untreated, it can lead to the destruction of the tissues that hold the teeth in place, ultimately resulting in tooth loss.

“This tooth loss can affect essential functions like chewing and speaking, while also affecting self-esteem,” says researcher Dr Fernando Valentim Bitencourt, from the Department of Dentistry and Oral Health, Aarhus University, Aarhus, Denmark. 

“As a result, periodontitis can significantly reduce a person’s quality of life, leading to difficulties with nutrition, communication, and social interactions.

“Understanding who is at higher risk, such as individuals with diabetes complications, is crucial for early intervention and prevention of these far-reaching effects.”

Some studies have found that individuals with microvascular complications of diabetes such as retinopathy (damage to the blood vessels of the retina) and neuropathy (damage to the nerves) are at higher risk of periodontitis. 

However, the results have been inconsistent and the studies have been small and have failed to take into account important confounding variables – factors such as sociodemographic status, smoking and diabetes duration – that can affect their outcome.

In addition, the joint impact of microvascular complications and dyslipidaemia (unhealthy levels of blood fats) has not been evaluated.

To address this, Dr Bitencourt and colleagues from Steno Diabetes Center Aarhus and National Dental Centre Singapore, analysed data on more than 15,000 individuals from the Health in Central Denmark study of people with type 2 diabetes.

The analysis involved 15,922 individuals (with a mean age of 63.7 years) with type 2 diabetes who had completed a questionnaire and a comprehensive laboratory examination.

The results, which were adjusted for potential confounding variables including sociodemographic status, lifestyle habits (including smoking and physical activity levels) and health conditions, found a clear link between microvascular complications and moderate/severe cases of periodontitis.

Individuals with diabetic retinopathy were 21% more likely to have moderate/severe periodontitis than those without complications of diabetes. 

Diabetic neuropathy was associated with a 36% increase in risk of having severe gum disease.  When the participants had both diabetic retinopathy and neuropathy, their likelihood of having moderate/severe periodontitis was 51% higher than in those without complications of diabetes.

The presence of dyslipidaemia further increased the odds of having moderate/severe periodontitis in those with diabetes complications.

Dr Bitencourt says: “When diabetes is poorly controlled high blood sugar levels can lead to inflammation which, over time, can affect the eyes, leading to retinopathy, or the nerves in the feet, causing neuropathy, or the gums, contributing to the development of severe periodontitis.

“Dyslipidaemia, which is very common, further increases the risk of severe gum disease.

“Importantly, the role of inflammation means that that periodontitis might not only serve as a marker for oral health issues but could also help identify individuals with a higher systemic inflammatory burden, who are therefore at greater risk of diabetes-associated microvascular complications.”

The researchers say that the take-home message for dentists and healthcare practitioners is clear: it is important to have a multidisciplinary approach when treating individuals with type 2 diabetes.

“For dentists, in particular, this means recognising that patients with type 2 diabetes and moderate/severe periodontitis, especially those with dyslipidaemia, may be at a higher risk for microvascular complications such as neuropathy and retinopathy,” says Dr Bitencourt. “Dentists should consider recommending that these patients be screened for microvascular complications.

“By working together, healthcare providers can help ensure that patients with type 2 diabetes, especially those who are at an elevated risk of diabetes complications, receive more comprehensive oral health care – potentially improving both their oral and overall health.”

First narrow-spectrum antibiotic successfully eliminates Fusobacterium nucleatum

 

F. nucleatum triggers the onset of gum disease, and is associated with colon cancer, pancreatic cancer, and Alzheimer’s disease

 

 The ADA Forsyth Institute, a leading oral health research organization, and Flightpath Biosciences Inc are excited to announce a groundbreaking discovery in the fight against severe gum disease and related systemic conditions. In a study published in the Journal of Oral Microbiology, ADA Forsyth scientists found that FP 100 (Hygromycin A), a first-in-class, small molecule, narrow-spectrum antibiotic, successfully eradicates Fusobacterium nucleatum without harming the oral or gut microbiomes. Fusobacterium is a key pathogen triggering the onset of periodontitis (gum disease), and its progression has been linked with many serious systemic diseases.

FP 100 as an effective treatment for Periodontitis

“This type of black and white data almost never happens,” said Alpdogan Kantarci, DDS, PhD, a senior scientist at ADA Forsyth who led the study. "The results were so clear. With FP 100, we can eliminate Fusobacterium nucleatum from the oral cavity, reverse tissue destruction and prevent disease progression without harming the beneficial microbiome." Lead authors, Dr. Nil Yakar Yilmaz and Dr. Ozge Unlu on Dr. Kantarci’s team, demonstrated the drug was effective both in vitro and in a mouse model of periodontal disease. Drs. Lujia Cen, Hatice Hasturk, Tsute Chen, Wenyuan Shi, and Xuesong He also contributed to this exciting research.

“The findings provide strong evidence that FP 100 could be a game-changer in the treatment of severe gum disease,” said Matt Tindall, Co-Founder and Chief Executive Officer of Flightpath Biosciences, Inc., the company funding the study at ADA Forsyth. “This antibiotic could work to prevent or treat advanced gum disease.”

Gum disease affects over 47% of individuals aged 30 and older, with the prevalence increasing to 60% in those aged 65 and older. The later stages of the disease are characterized by progressive destruction of jawbone tissue and can lead to tooth loss. Current treatments focus on slowing the progression of the disease, but most of these are not covered by dental insurance. There is no available cure.

A New Era in Antibiotic Development

One of the most exciting findings in this study is that the antibiotic is effective at targeting just Fusobacteria without harming beneficial bacteria necessary for maintaining human health. Periodontal disease has long been a challenge to treat effectively because antibiotics typically wipe out both harmful and beneficial bacteria.

“Often, antibiotics treating that disease will also kill all the bacteria that aid in preventing overpopulation of pathogens,” said Dr. Kantarci. “With the increase of antibiotic-resistant superbugs, being able to kill a dangerous pathogen with a narrow-spectrum antimicrobial drug candidate represents a significant paradigm shift in antibiotic development. Eliminating that key pathogen is a very important strategy to control the disease.”

Implications for Systemic Health

The potential impact of this antibiotic extends far beyond the mouth, potentially preventing the development of serious chronic diseases, including heart disease, colon and pancreatic cancers, Alzheimer's disease, preterm birth, inflammatory bowel disease, and rheumatoid arthritis.

“Fusobacterium is an insidious pathogen,” said Dr. Kantarci. “Studies show it can travel from the oral cavity to other places, where it colonizes and causes disease. We recently published a study showing that Fusobacterium can enter human cells like a Trojan horse and travel undetected to other parts of the body where they colonize and cause disease. Eliminating the bacteria early in the oral cavity is also systemic prevention.”

This promising antibiotic candidate, FP 100 (hygromycin A), was rediscovered by a team of researchers led by Kim Lewis, PhD, Northeastern University, who focused on its ability to target the bacterium Borelliella burgdorferi, which causes Lyme Disease.

Looking Ahead

ADA Forsyth and Flightpath Bio have filed a joint patent application for FP 100. They plan to explore the antibiotic's potential further in clinical trials and expand its application to other conditions caused by Fusobacterium nucleatum. "We are entering a new frontier in both local and systemic disease prevention," said Dr. Kantarci. "The ability to selectively target harmful bacteria while preserving the beneficial microbiome opens the door to innovative treatments that could significantly improve patient outcomes."

Paper cited: “Targeted elimination of Fusobacterium nucleatum alleviates periodontitis,” Journal of Oral Microbiology. DOI: #10.1080/20002297.2024.2388900