Titanium micro-particles in the oral mucosa around dental implants are common. This is shown in a new study from the University of Gothenburg, which also identified 14 genes that may be affected by these particles.
According to the researchers, there is no reason for concern, but more knowledge is needed.
“Titanium is a well-studied material that has been used for decades. It is biocompatible and safe, but our findings show that we need to better understand what happens to the micro-particles over time. Do they remain in the tissue or spread elsewhere in the body?” says Tord Berglundh, senior professor of periodontology at Sahlgrenska Academy, University of Gothenburg.
Found at all implants
Previous research has shown that titanium particles may occur in inflamed tissues around dental implants. The new study, published in Communications Medicine, showed that titanium micro-particles were consistently found at all examined implants—even those without signs of inflammation.
The researchers analysed tissue samples from 21 patients with multiple adjacent implants. Samples were taken both at healthy implants and at implants affected by peri-implantitis, an inflammatory disease in the tissue around the implant. Each patient thus served as their own control. The density of particles varied between patients, but not between sites with and without peri-implantitis within the same patient. The analyses were conducted in collaboration with Uppsala University, where researchers used an advanced method called µ-PIXE to map the distribution of titanium particles in the tissue samples.
Affected genes
Peri-implantitis is a microbial biofilm-associated inflammatory disease around dental implants, with features similar to those of periodontitis around teeth. The inflammatory process is complex and the resulting destruction of supporting bone in peri-implantitis may lead to loss of the implant.
“We observed that tissue samples with higher concentrations of titanium particles had an altered gene expression, especially genes related to inflammation and wound healing. We identified 14 such genes, but it is unclear whether the particles influence the local immune response or if the difference in gene expression reflects inter-individual variability in inflammatory conditions,” says Carlotta Dionigi, specialist in periodontology and researcher at the Department of Periodontology, Sahlgrenska Academy, University of Gothenburg.
The researchers suspect that titanium particles are released during the surgical installation procedure, when the screw-shaped implant is inserted into the prepared canal in the alveolar bone. In this context, the observation on differences in micro-particle densities between various implant systems deserves attention, since the surface structure of the implant may influence the deposition of micro-particles. This is now an important topic for continued research.
South Africa’s burden of oral diseases is not only inextricably linked to non-communicable diseases but also presents an urgent public health challenge, with rising concern over its impact on mental health.
Oral diseases are a major health concern for many countries and negatively impacts people throughout their lives. Oral diseases lead to pain and discomfort, social isolation and loss of self-confidence, and they are often linked to other serious health issues. And yet, there is no reason to suffer: most oral health conditions are preventable and can be treated in their early stages.
Globally, every year on March 20, World Oral Health Day is commemorated with the aim to empower people with the knowledge, tools, and confidence to secure good oral health.
This year, the Day’s focus shifts to the mind-mouth connection, with the tagline from the FDI World Dental Federation: “A Happy Mouth Is… A Happy Mind”. This campaign aims to raise awareness of how poor oral health can negatively impact quality of life, highlighting the importance of a healthy mouth for mental well-being.
Macelle Erasmus, Head of Expert at Haleon South Africa – a leader in consumer health and self-care, says, “Oral health is not just about bright smiles and good-looking teeth – it is a critical component of overall well-being. In South Africa, the high prevalence of oral diseases, particularly among children and vulnerable communities, reinforces the urgent need for improved oral health education and preventive care.”
Haleon’s leading oral health brands Aquafresh and Sensodyne, are committed to improving oral health education and access across the country.
Over the course of just three months, we have conducted more than 39,000 gum health screenings across 16 clinics. In 2025, our expansion aims to reach 100,000 underserved communities as part of Haleon’s oral health care outreach programs.
According to the South African Dental Association (SADA), 41% of children aged 1-9 years and close to 28% of people aged 5 years and over experienced untreated tooth decay in milk and permanent teeth respectively, while nearly 25% of people aged 15 years and over experienced severe periodontal disease in 2019. The country also saw 1,933 new cases of lip and oral cavity cancer in 2020.
The World Health Organisation’s Global Strategy and Action Plan on Oral Health 2023–2030, explains that oral health encompasses a range of diseases and conditions. The most prevalent public health issues include dental caries, severe periodontal (gum) disease, complete tooth loss (edentulism), oral cancer, oro-dental trauma, noma and congenital malformations such as cleft lip and palate, most of which are preventable.
The main oral diseases and conditions are estimated to affect close to 3.5 billion people worldwide. These conditions combined have an estimated global prevalence of 45%, which is higher than the prevalence of any other NCD.
However, oral diseases and conditions share risk factors common to the leading NCDs, including all forms of tobacco use, harmful alcohol use, high intake of free sugars and lack of exclusive breastfeeding.
The Department of Health’s National Oral Health Policy and Strategy 2024-2034 acknowledges that oral health is poorly integrated in other health programmes, “though it is an integral part of general health.” It further recognises that: “Its role in management and care of communicable diseases, genetic disorders, trauma, injury, and violence is often overlooked.”
This integration is particularly important as more than three million patients are treated in the country’s public primary healthcare facilities annually, at a cost of R650 million. Addressing oral health holistically – within the broader healthcare system – can significantly reduce this burden.
It’s common knowledge that sugar causes cavities, but new research provides evidence that – depending on your genetic makeup – starches could also be a contributing factor.
The study, published in Microorganisms, explores the response of the oral microbiome to starch, finding that the number of copies of a particular gene, AMY1, in combination with starch, alters the complex composition of bacteria that play a role in oral health.
“Most people have been warned that if you eat a bunch of sugar, make sure you brush your teeth,” said Angela Poole, senior author and assistant professor of molecular nutrition in the College of Agriculture and Life Sciences and the College of Human Ecology. “The takeaway finding here is that depending on your AMY1 copy number, you may want to be just as vigilant about brushing your teeth after eating those digestible starches.”
Researchers, including first author Dorothy Superdock, PhD ’23, collected saliva samples from 31 subjects with a range of AMY1 copy numbers – copies of the AMY1 gene in the DNA – and added starch to the cultured samples, or biofilms, to see how the bacterial makeup changed. They found that, in general, the diversity of bacteria decreased when starch was added. For those samples with high numbers of AMY1, the starch significantly reduced the proportions of two bacteria, Atopobium and Veillonella, while Streptococcus appeared to increase.
All three bacteria are associated with tooth decay or gum disease, Poole said.
“Some increased and some decreased, so it’s not so straightforward as saying, ‘The whole thing is good or bad,’” Poole said. “It’s an interaction, but it looks like the AMY1 copy number, as well as which species are present in people’s mouths when they eat starch, is affecting the risk for developing these diseases.”
AMY1 codes for the salivary amylase enzyme, which helps break down starch in the mouth. Previous studies have associated AMY1 with cavities and periodontal disease. Poole, in prior studies, found that a high AMY1 copy number is associated with higher levels of the species Porphyromonas endodontalis, which is strongly associated with periodontitis and gum disease.
But how the salivary amylase enzyme interacts with its main substrate, starch, to alter the oral microbiome and increase disease risk was unclear.
“That’s what we wanted to know in this experiment,” Poole said. “What’s going on in the mouth if someone eats starch, and is the answer different if their copy number is high or if it’s low? What we found was that there are other bacteria involved in these processes and that the changes depended on AMY1.”
The researchers also found evidence that the oral microbiome has co-evolved in response to increasing copies of AMY1, which is found in higher numbers in populations where there’s a long history of agriculture and starch consumption. In the pool of 31 samples, taken locally in Ithaca, the AMY1 number ranged from two to 20 copies.
“The populations that historically had greater access to starch tend to have more copies,” Poole said, “which makes sense from a practical standpoint, because it would have given you a survival advantage when food is scarce, to be able to break down those starches more efficiently.”
In saliva samples with a high AMY1 copy number, the researchers saw increased populations of bacteria, like Streptococcus, that feed off the starch’s sugars.
“If someone has a high copy number, they break down starch efficiently, and bacteria that like those sugars are going to grow more in that person’s mouth,” Poole said. “So you can have species behave differently based on the different substrates. It’s pretty incredible – how we adapt and these microbes turn around and adapt, too.”
Flossing your teeth at least once a week may be linked to a lower risk of stroke caused by blood clotting and atrial fibrillation, according to a preliminary study to be presented at the American Stroke Association’s International Stroke Conference 2025. The meeting is in Los Angeles, Feb. 5-7, 2025, and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.
“A recent global health report revealed that oral diseases – such as untreated tooth decay and gum disease – affected 3.5 billion people in 2022, making them the most widespread health conditions,” said study lead author Souvik Sen, MD, MS, MPH, chair of the Department of Neurology, Prisma Health Richland Hospital and the University of South Carolina School of Medicine in Columbia, South Carolina. “We aimed to determine which oral hygiene behaviour – dental flossing, brushing or regular dentist visits – has the greatest impact on stroke prevention.”
The Atherosclerosis Risk in Communities (ARIC) study, one of the first large-scale investigations of this kind in the US, assessed the home use of dental floss through a structured questionnaire of more than 6000 people. Among those who reported flossing, 4092 had not experienced a stroke, and 4050 had not been diagnosed with atrial fibrillation (AFib).
Participants were asked about their status regarding high blood pressure, diabetes, high cholesterol, smoking, body mass index, education, regular brushing and dentist visits. During the 25 years of follow-up, 434 participants were identified as having strokes, of which 147 were larger artery brain clots, 97 were heart-driven clots and 95 were hardening of the smaller arteries. Additionally, 1291 participants were noted to have experienced AFib.
The analysis found:
Flossing was associated with a 22% lower risk of ischaemic stroke, 44% lower risk of cardioembolic stroke (blood clots traveling from the heart) and 12% lower risk of AFib.
The associated lower risk was independent of regular brushing and routine dental visits or other oral hygiene behaviours.
Increasing the frequency of flossing had a greater chance of stroke risk reduction.
Flossing was also associated with a lower chance of cavities and periodontal disease.
Researchers were surprised by the reduction of irregular heartbeats, or AFib. AFib is the most common form of irregular heartbeat. It can lead to stroke, heart failure or other cardiovascular complications.
“Oral health behaviours are linked to inflammation and artery hardening. Flossing may reduce stroke risk by lowering oral infections and inflammation and encouraging other healthy habits,” Sen said. “Many people have expressed that dental care is costly. Flossing is a healthy habit that is easy to adopt, affordable and accessible everywhere.”
Study limitations include that data were based on answers to a questionnaire, and the 25-year follow-up appears to have focused on stroke and heart outcomes only. There was no follow-up concerning flossing or other oral behaviours over the years, Sen said.
A combination of acetaminophen and ibuprofen controls pain after wisdom tooth removal better than opioids, according to a Rutgers Health study that could change how dentists treat post-surgical pain.
The trial in more than 1800 patients found that those given a combination of ibuprofen and acetaminophen experienced less pain, better sleep and higher satisfaction compared with those receiving the opioid hydrocodone with acetaminophen.
“We think this is a landmark study,” said Cecile Feldman, dean of Rutgers School of Dental Medicine and lead author of the study, which was published in the The Journal of American Dental Association. “The results actually came in even stronger than we thought they would.”
Dentists, who rank among the US’ leading prescribers of opioids, wrote more than 8.9 million opioid prescriptions in 2022. For many young adults, dental procedures such as wisdom tooth extraction are their first exposure to opioid medications.
“There are studies out there to show that when young people get introduced to opioids, there’s an increased likelihood that they’re going to eventually use them again, and then it can lead to addiction,” said study co-investigator Janine Fredericks-Younger.
To compare opioid and non-opioid pain relief, the researchers conducted a randomised trial on patients undergoing surgical removal of impacted wisdom teeth, a common procedure that typically causes moderate to severe pain.
Half the patients received hydrocodone with acetaminophen. The other half got a combination of acetaminophen and ibuprofen. Patients rated their pain levels and other outcomes, such as sleep quality, over the week following surgery.
Results showed the non-opioid combination provided superior pain relief during the peak-pain period in the two days after surgery. Patients taking the non-opioid medications also reported better sleep quality on the first night and less interference with daily activities throughout recovery.
Patients who received the over-the-counter combo were only half as likely as the opioid patients to require additional “rescue” pain medication. They also reported higher overall satisfaction with their pain treatment.
“We feel pretty confident in saying that opioids should not be prescribed routinely and that if dentists prescribe the non-opioid combination, their patients are going to be a lot better off,” Feldman said.
The study’s size and design make it particularly notable. With more than 1,800 participants across five clinical sites, it’s one of the largest studies of its kind. It also aimed to reflect real-world medication use rather than the tightly controlled conditions of many smaller pain studies.
“We were looking at the effectiveness – so how does it work in real life, taking into account what people really care about,” said Feldman, referring to the study’s focus on sleep quality and the ability to return to work.
The findings align with recent recommendations from the American Dental Association to avoid opioids as first-line pain treatment. Feldman said she hopes they will change prescribing practices.
“For a while, we’ve been talking about not needing to prescribe opioids,” Feldman said. “This study’s results are such that there is no reason to be prescribing opioids unless you’ve got those special situations, like medical conditions preventing the use of ibuprofen or acetaminophen.”
Members of the research team said they hope to expand their work to other dental procedures and pain scenarios. Other researchers at the school are testing cannabinoids for managing dental pain.
“These studies not only guide us on how to improve current dental care,” said Feldman, “but also on how we can better train future dentists here at Rutgers, where we constantly refine our curriculum the light of science.”
Researchers from Japan have discovered a certain oral bacteria associated with rheumatoid arthritis causes inflammation, through macrophages and an inflammatory enzyme, caspase-11. Their results appear in the International Journal of Oral Science.
Periodontal disease, which affects the gums and tissues that surround the teeth, is one of the most prevalent dental conditions worldwide, and besides tooth loss is associated with other health effects. Over the past few decades, clinical studies have revealed that the periodontal pathogen Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is closely related to the onset and worsening of rheumatoid arthritis (RA), a serious autoimmune disease that affects joints. However, what goes down at the molecular level remains largely unexplored and unclear.
In this study, a research team from Tokyo Medical and Dental University (TMDU) in Japan sought to fill this knowledge gap through detailed mechanistic studies in an animal model.
First, the researchers conducted preliminary experiments to confirm whether A. actinomycetemcomitans infection influenced arthritis in mice. To this end, they used the collagen antibody-induced arthritis mouse model, which is a well-established experimental model that mimics several aspects of RA in humans. They found that infection with this specific bacterium led to increased limb swelling, cellular infiltration into the lining of the joints, and higher levels of the inflammatory cytokine interleukin-1β (IL-1β) within the limbs.
Notably, these symptoms of worsening RA could be suppressed by administering a chemical agent called clodronate that depletes macrophages. This demonstrated that macrophages were somehow involved in aggravating RA caused by A. actinomycetemcomitans infection.
Further investigation using macrophages derived from mouse bone marrow revealed that A. actinomycetemcomitans infection increased the production of IL-1β. In turn, this triggered the activation of a multiprotein complex known as the inflammasome, which plays a key role in initiating and modulating the body’s inflammatory response to infections.
The researchers added yet one more piece to this puzzle using caspase-11-deficient mice. In these animals, inflammasome activation due to A. actinomycetemcomitans was suppressed. Most importantly, caspase-11-deficient mice exhibited less deterioration of arthritis symptoms, hinting at the important role that caspase-11 plays in this context. “Our research findings provide new insights into the link between periodontal pathogenic bacteria and the exacerbation of arthritis through inflammasome activation, offering important information on the long-debated relationship between periodontal disease and systemic diseases,” highlights Professor Toshihiko Suzuki, one of the lead authors of the study.
With any luck, these efforts will contribute to the development of novel therapeutic strategies to manage RA. “The findings of this research may pave the way for advances in clinical treatments for RA induced by infection with A. actinomycetemcomitans. Our suggestion to inhibit inflammasome activation could attenuate the expansion of inflammation to joints, resulting in a recovery from arthritis symptoms,” says lead author Dr Tokuju Okano. “Moreover, the outcome of our work could contribute to the development of treatment strategies for not only arthritis but also other systemic diseases, such as Alzheimer’s disease, which is also related to periodontal pathogenic bacteria,” he predicts.
Photo by Towfiqu barbhuiya: https://www.pexels.com/photo/a-toothbrush-with-toothpaste-on-a-white-surface-12065623/
A new study by investigators from Brigham and Women’s Hospital examined whether daily toothbrushing among hospitalised patients is associated with lower rates of hospital-acquired pneumonia and other outcomes. Their analysis of 15 randomised clinical trials found that hospital-acquired pneumonia rates were lower among patients who received daily toothbrushing compared to those who did not. The results were especially compelling among patients on mechanical ventilation. Their results are published in JAMA Internal Medicine.
“The signal that we see here towards lower mortality is striking – it suggests that regular toothbrushing in the hospital may save lives,” said corresponding author Michael Klompas, MD, MPH, hospital epidemiologist and an infectious disease physician in the Department of Medicine at BWH and Professor of Population Medicine at Harvard Pilgrim Health Care Institute.
“It’s rare in the world of hospital preventative medicine to find something like this that is both effective and cheap. Instead of a new device or drug, our study indicates that something as simple as brushing teeth can make a big difference.”
Hospital-acquired pneumonia occurs when bacteria in the mouth enter a patient’s airways and infect their lungs.
Patients experiencing frailty or patients with a weakened immune system are particularly susceptible to developing hospital-acquired pneumonia during their hospital stay.
However, adopting a daily toothbrushing regimen can decrease the amount of bacteria in the mouth, potentially lowering the risk of hospital-acquired pneumonia from occurring.
The team conducted a systematic review and meta-analysis to determine the association between daily toothbrushing and hospital-acquired pneumonia.
Using a variety of databases, the researchers collected and analysed randomised clinical trials from around the world that compared the effect of regular oral care with toothbrushing versus oral care without toothbrushing on the occurrence of hospital-acquired pneumonia and other outcomes.
The team’s analysis found that daily toothbrushing was associated with a significantly lower risk for hospital-acquired pneumonia and ICU mortality.
In addition, the investigators identified that toothbrushing for patients in the ICU was associated with fewer days of mechanical ventilation and a shorter length of stay in the ICU.
Most of the studies in the team’s review explored the role of a teeth-cleaning regimen in adults in the ICU.
Only two of the 15 studies included in the authors’ analysis evaluated the impact of toothbrushing in non-ventilated patients.
The researchers are hopeful that the protective effect of toothbrushing will extend to non-ICU patients but additional studies focusing on this population are needed to clarify if in fact this is the case.
“The findings from our study emphasise the importance of implementing an oral health routine that includes toothbrushing for hospitalised patients. Our hope is that our study will help catalyse policies and programs to assure that hospitalised patients regularly brush their teeth. If a patient cannot perform the task themselves, we recommend a member of the patient’s care team assist,” said Klompas.
On the 2nd of January 2024, Simphiwe*, needing emergency oral healthcare, turned to the Cala District Hospital in the Eastern Cape. However, she was confronted with a note on the door that read, “Dear Community Members, starting from the 18th of December 2023 to the 12th of January 2024 there is no dentist. The dentist will start working on the 15th of January 2024.”
Many such notices hang in front of oral health clinic doors, mostly where dentists work alone to respond to the myriad of emergency oral health needs within their catchment area. Having previously worked alone at a provincial government funded hospital in the rural Eastern Cape, similar notices would be placed on the door to the oral health clinic I operated, until such time as a colleague joined me at the facility.
Oral diseases affect more than 3 billion people globally, while in Africa, it affects an estimated 400 million people.
Oral diseases and conditions that affect people include trauma-related oral injuries, oral cancers, dental decay, and periodontal disease amongst others.
While dental decay remains the most common form of oral disease, untreated, it can lead to life-threatening complications. The closure of dental services at any oral health clinic may subject people to the risk of developing conditions such as Ludwig’s angina, a life-threatening condition that is linked to delayed access to care.
Fewer than 200 dentists
The Eastern Cape is predominantly a rural province, with most of the province’s 7.2 million people largely depending on public healthcare services for the majority, if not all their healthcare needs. The province employs fewer than 200 dentists, a majority of whom are concentrated in the more urban/peri-urban centres.
Cala, a rural town in the province’s Sakhisizwe Local Municipality, is home to an estimated 63 000 people and Cala District Hospital provides access to oral health services to this population. The hospital’s closed dental clinic over the festive period deprived the people of Cala of much-needed care.
It is well known that the festive period results in an increased need for emergency healthcare, including oral healthcare services. People often present with jaw fractures, tooth fractures -often a result of violence or accidents associated with an increase in alcohol consumption -, oral pain and sepsis. While the festive period may result in the increased need for managing these conditions, these are the usual conditions, amongst others, that are managed in many public oral health clinics in most provinces.
Oral health professionals, in particular dentists, are trained to manage the complete spectrum of general oral diseases and often refer to dental specialists for complex and specialised management. In a province like the Eastern Cape, characterised by a dire shortage of dental specialists, dentists are the last defence for many of the people in the province.
A significant portion of dentists in the province work alone, with limited options to manage their leave, often leaving clinics closed in their absence.
However, the closure of dental clinics without a detailed and well-communicated plan is unacceptable and places the lives of populations in danger. At times, people have been known to resort to harmful and dangerous home practices to relieve themselves of their anguish.
We need a plan
A comprehensive plan must be put in place for efficient management and referral of emergency oral healthcare cases during the festive period so that we avoid a repeat of this year’s unacceptable situation at Cala District Hospital 12 months down the line. People in need of oral health services must be made aware of where they can access such services without any delay.
Beyond this, there is a need to invest in building adequate human resource capacity for oral health in the province, to ensure that services are readily available. A mix of oral health professionals and the prioritisation of “lone dentist” clinics for community service placements should help alleviate some of the problems in the system.
It is concerning that the challenges faced in the Eastern Cape is very similar to those in other parts of the country. Fewer than 3000 dentists are working in the public healthcare sector nationwide. With such numbers it is unlikely that what happened to Simphiwe was an isolated incident. Her experience should serve as an important case study, highlighting the significant problems faced by communities and oral health professionals.
Those responsible for managing oral healthcare services in South Africa must take note and recognise that the continued deprioritisation and neglect of the population’s oral health cannot be allowed to continue. We must work together to ensure that oral health is given the attention it deserves as a critical aspect of general health and well-being.
*Dr Vava is the President of the Public Oral Health Forum, a network of public oral health professionals striving for oral health equity, dignity and well-being for all.
The Vikings, famous as raiders who terrorised many parts of Europe, may have been quite ruthless, but their society seems to have had access to surprisingly advanced dental care for the era. A University of Gothenburg analysis of Viking Age teeth showed that although caries and toothache were widespread, there was also evidence of dental practices not too dissimilar from modern ones.
The study examined 3293 teeth from 171 individuals among the Viking Age population of Varnhem in Västergötland, Sweden.
The site is known for extensive excavations of Viking and medieval environments, including tombs where skeletons and teeth have been preserved well in favourable soil conditions.
The research team from the University of Gothenburg’s Institute of Odontology worked with an osteologist from Västergötland’s Museum. The skulls and teeth underwent clinical examinations at Gothenburg using standard dentistry tools under bright light.
A number of X-ray examinations were also performed using the same technique used in dentistry, where the patient bites down on a small square imaging plate in the mouth.
Caries and tooth loss
The results, which have been published in the journal PLOS ONE, show that 49% of the Viking population had one or more caries lesions.
Of the adults’ teeth, 13% were affected by caries – often at the roots. Children with milk teeth or a mix of milk and adult teeth, were entirely caries-free however. (Presumably sweets for the kids were not high on the Viking raiders’ lists.)
Tooth loss was also common among adults. The studied adults had lost an average of 6% of their teeth, excluding wisdom teeth, over their lifetimes. The risk of tooth loss increased with age.
The findings suggest that caries, tooth infections, and toothache were common among the Viking population in Varnhem – but the study also reveals examples of tooth care.
“There were several signs that the Vikings had modified their teeth, including evidence of using toothpicks, filing front teeth, and even dental treatment of teeth with infections,” says Carolina Bertilsson, a dentist and Associate Researcher, and the study’s first-named and corresponding author.
Not unlike today’s treatments
One sign of more sophisticated procedures was molars with filed holes, from the crown of the tooth and into the pulp, probably in order to relieve pressure and alleviate severe toothache due to infection.
“This is very exciting to see, and not unlike the dental treatments we carry out today when we drill into infected teeth. The Vikings seem to have had knowledge about teeth, but we don’t know whether they did these procedures themselves or had help.”
The filed front teeth may have been a form of identity marker. In both this and previous studies, the cases found were male.
Carolina Bertilsson continues: “This study provides new insights into Viking oral health, and indicates that teeth were important in Varnhem’s Viking culture. It also suggests that dentistry in the Viking Age was probably more sophisticated than previously thought.”
In one of every 10 people, and in one third of children with celiac disease, the enamel coating of the teeth appears defective, failing to protect the teeth properly. As a result, teeth become more sensitive to heat, cold and sour food, and they may decay faster. In most cases, the cause of the faulty enamel production is unknown.
Now, a study by Prof Jakub Abramson and his team at the Weizmann Institute of Science, published recently in Nature, may shed light on this problem by revealing a new children’s autoimmune disorder that hinders proper tooth enamel development. The disorder is common in people with a rare genetic syndrome and in children with celiac disease. These findings could help develop strategies for early detection and prevention of the disorder.
Tooth enamel is made up primarily of mineral crystals that are gradually deposited on protein scaffolds during enamel development. Once the crystals are in place, the protein scaffold is dismantled, leaving behind a thin, exceptionally hard layer of enamel. A strange phenomenon was identified in people with a rare genetic disorder known as APS-1: although the enamel layer of their milk teeth forms perfectly normally, something causes its faulty development in their permanent teeth. Since people with APS-1 suffer from a variety of autoimmune diseases, Abramson and his team hypothesised that the observed enamel defects may also be of an autoimmune nature
In autoimmune disease, to prevent T cells from triggering the immune system to attack body tissues, T cells developing in the thymus gland must be educated’ to discriminate between the body’s own proteins and those of foreign origin. To this end, T cells are presented with short segments of self-proteins that make up various tissues and organs in the body. When a ‘poorly educated’ T cell erroneously identifies a self-protein in the thymus as a target for attack, that T cell is labelled as dangerous and destroyed, so that it could not cause any damage after being released from the thymus.
This critical education step is impaired in APS-1 patients as a result of a mutation in a gene known as the autoimmune regulator (Aire). This gene is essential for the T cell education process: It produces a protein that is responsible for the collection of self-proteins presented to the T cells in the thymus. In their new study, scientists from Abramson’s lab in Weizmann’s Immunology and Regenerative Biology Department, led by research student Yael Gruper, sought to work out how mutations in the Aire gene lead to deficient tooth enamel production. The researchers discovered that, in the absence of Aire, proteins that play a key role in the development of enamel are not presented to the T cells in the thymus gland. As a result, T cells that are liable to identify these proteins as targets are released from the thymus, and they encourage the production of antibodies to the enamel proteins. But why do these autoantibodies damage permanent teeth and not baby teeth?
The answer to this question lies in the fact that milk teeth develop in the embryonic stage, when the immune system is not yet fully formed and cannot create autoantibodies. In contrast, the development of enamel on permanent teeth starts at birth and continues until around the age of six, when the immune system is sufficiently mature to thwart enamel development. Furthermore, the researchers found a correlation between high levels of antibodies to enamel proteins and the severity of the harm to enamel development in children with APS-1. This strengthens the assumption that the presence of enamel-specific autoantibodies in childhood can potentially lead to dental problems.
When the researchers looked into deficiencies in enamel development in people with other autoimmune diseases, they found a very similar phenomenon in children with celiac disease, a relatively common autoimmune disorder that affects around 1% of people in the West. When people with this disease are exposed to gluten, their immune system attacks and destroys the cellular layer lining the small intestine, leading to attacks on other self-proteins in the intestine.
In an attempt to understand how celiac disease, known to cause intestinal damage, may also cause damage to tooth enamel, the researchers first examined whether people with this disease have autoantibodies against enamel. They found that a large proportion of celiac patients have these autoantibodies, just as do people with APS-1. But the ‘education’ in the thymus gland of these patients seems normal, so why do they develop these antibodies? The researchers hypothesised that some proteins are found in both the intestine and the dental tissue and that these proteins play an important role in the development of tooth enamel. In this case, the antibodies that identify proteins in the intestine might move through the bloodstream to the dental tissue, where they could start to disrupt the enamel production process.
Since many celiac patients had previously been found to develop sensitivity to cow’s milk, the researchers decided to focus on the k-casein protein, a major component of dairy products. Strikingly, they found that the human equivalent of k-casein is one of the main components of the scaffold necessary for enamel formation. This led them to hypothesise that antibodies produced in the intestines of celiac patients in response to certain food antigens, such k-casein, may subsequently cause collateral damage to the development of enamel in the teeth, similarly to the way in which antibodies against gluten can eventually trigger autoimmunity against the intestine.
Indeed, they discovered that most of the children diagnosed with celiac had high levels of antibodies against k-casein from cows’ milk, which in many cases can also react against k-casein’s human equivalent expressed in the enamel matrix. This means that in theory, the same antibodies that are produced in the intestine against the milk protein could act against the human k-casein in the teeth.
These findings could have implications for the food industry. “Similarly to the lessons learned from gluten, we can assume that the consumption of large quantities of dairy products could lead to the production of antibodies against k-casein,” Abramson explains. “This protein increases the amount of cheese that can be produced from milk, so the dairy industry deliberately raises its concentration in cow’s milk. Our study, however, found that the milk k-casein is a potent immunogen, which may potentially trigger an immune response that can harm the body itself.”
Tooth enamel flaws are common, not just among people with celiac disease or APS-1. “Many people suffer from impaired tooth enamel development for unknown reasons,” Abramson says. “It is possible that the new disorder we discovered, along with the possibility of diagnosing it in a blood or saliva test, will give their condition a name. Most important, early diagnosis in children may enable preventive treatment in the future.”
