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

 

image: 

Improving periodontal inflammation by glycemic control treatment

view more 

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."

###

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

From cavities to sleep apnea: dentists can assume new role in saving lives

A patient dozes off in a dental chair despite the anxiety of an impending procedure. A seemingly unremarkable act but — for dentists versed in the latest sleep research — this red flag hints at a life-threatening condition.

In a research review published in the Journal of the American Dental Association, Rutgers Health researchers identified dentists as an unexpected player in the battle against life-threatening sleep disorders.

The review suggests dental professionals have unique opportunities to screen for conditions such as obstructive sleep apnea, a disorder that affects millions of Americans and is linked to serious health risks, including cardiovascular disease and neurodegeneration.

It also challenges dentists to look beyond teeth and gums to the broader landscape of patient health.

"We have a great opportunity to change lives for the better," said Davis Thomas, a clinical associate professor at the Rutgers School of Dental Medicine and senior author of the review. "Dentists can be the first line of defense in identifying sleep disorders. They often see symptoms long before physicians. Indicators like tooth grinding, tongue scalloping or even a patient dozing off in the chair can be early signs that something more is going on."

Sleep disorders such as obstructive sleep apnea affect more than half of Americans at some point in their lives. Many cases go undiagnosed, but dentists can play an important role in reducing those numbers.

The review outlines several key indicators that dental clinicians should look for during examinations, including enlarged jaw muscles, scalloped tongue edges, white lines on the cheeks, restricted visibility of the throat, dental wear patterns and tiny cracks on teeth.

These physical signs, combined with patient history and simple screening tools, can help dentists identify at-risk patients with up to 80 percent accuracy.

"It's not just about looking at teeth anymore," Thomas said. "We need to observe the whole patient, from their behavior in the waiting room to the subtle signs in their oral cavity."

Another sign of concern, according to the review authors, is bruxism, commonly known as teeth grinding. Contrary to long-held beliefs, the studies suggest teeth griding is often a symptom of underlying sleep issues rather than a standalone problem caused by dental misalignment.

"We've been treating the symptoms without addressing the root cause for far too long," Thomas said. "By understanding the neuroscience behind sleep disorders, we can provide more comprehensive care and potentially prevent serious health complications."

This shift in perspective could have far-reaching implications. By identifying patients at risk for sleep disorders, dentists can facilitate early intervention, potentially preventing complications such as hypertension, heart disease and stroke.

To implement these findings, Thomas and his team propose a simple protocol for dental practices: Incorporate sleep-related questions into patient history forms. Other recommendations include training dental staff to recognize physical signs of sleep disorders and using validated screening tools like the STOP-BANG (snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck size, gender) questionnaire, which screens for obstructive sleep apnea and establish referral networks with sleep medicine specialists.

"We're not asking dentists to diagnose sleep disorders," Thomas said. "We're asking them to recognize the signs and make appropriate referrals. This simple act can be lifesaving."

Thomas recommends that dentists looking to incorporate sleep screening into their practices start with education.

"Attend sleep medicine conferences, take continuing education courses, and stay up-to-date with the latest research," he said. "The more we learn, the more we realize how much we don't know – and how much we can do to help our patients."