Immune deficiency explains rampant caries in some children

                    

Researchers at Umeå University in Sweden have made a novel discovery connecting genetic innate immunity deficiencies to rampant caries and increased risk of dental caries affecting about one in five children. The results could lead to a better way of identifying high-risk patients and treat their caries. The study has been published in the journal EBioMedicine.

In a five-year study, in which saliva and isolated bacterial strains from a large number of children was analyzed and the dental health monitored, the research group recently established that some high-risk children have a more virulent variant of the caries bacterium Streptococcus mutans. The same research group now shows that high-risk children also have genetic defects in innate and adaptive immunity, making them more vulnerable against oral bacteria and streptococci in general.

"Most people consider caries to be a lifestyle condition caused by bad eating- and oral hygiene routines that lead to acidic pH levels in the mouth, which in turn damage the enamel and promote the colonization of acid-producing bacteria such as S. mutans," says Nicklas Strömberg, professor and Head at the Department of Cariology at Umeå University and Västerbotten County Council, and first author of the article.

"Our results now show that this correlation is accurate for approximately four out of five individuals, who have a small-to-moderate risk of developing caries because their composition of salivary innate immunity proteins make them relatively resistant to caries. However, we have shown that so-called high-risk individuals, which are about one in five individuals, carry a genetically different composition of the same salivary innate immunity proteins, making them highly susceptible to caries independent of eating- or oral hygiene habits or S. mutans-infection."

One in five children in Sweden is considered a high-risk individual when it comes to the risk of developing dental caries. These high-risk individuals do not respond to traditional caries prevention or treatment, and bio markers cannot predict future risk of caries in the group. Chronic caries infection and missing teeth are also risk factors for systemic diseases such as stroke and cardiovascular diseases.

Innate and adaptive immunity deficiencies explain high-risk individuals for caries

A research group led by Nicklas Strömberg have in the current study followed 452 children (between ages 12 and 17) in Västerbotten over a five year period. After genetic analysis of their DNA, the children were divided into various risk groupings based on genetic variation in PRH1 and PRH2, encoding salivary acidic proline-rich proteins. At a five-year follow-up, the researchers could see how caries had developed in the various risk groupings.

The results showed that children with high susceptibility or risk for caries had defective proteins in their saliva. The defective salivary proteins in question were acidic and basic proline-rich proteins and the adhesive protein salivary agglutinin (or DMBT1). According to the researchers, the defective proteins probably fail to mediate the same innate and adaptive immunity responses that serve to protect individuals with small-to-moderate caries risk from the oral bacterial flora.

The researchers describe how allelic variation in PRH1 and PRH2, encoding acidic proline-rich proteins, separate children into different caries susceptibility or risk groupings. As expected, children with a low-to-moderate susceptibility or risk for caries along with a genetically intact set of proteins were found to develop caries from bad eating and oral hygiene routines and S. mutans-infection.

However, the children with high susceptibility develop caries independent of eating- or oral hygiene routines or S. mutans-infection but from the immune deficiency. Accordingly, when children were treated with dental braces the high risk children exclusively developed several times more caries after 5 years. The researchers believe this is due to plaque accumulation and impaired saliva flow as a result from the dental braces.

"This new knowledge about genetic susceptibility groupings could be used to improve individualized dental care. Children in the higher risk group could then be diagnosed before caries lesions and symptoms arise. In this way, prevention could be implemented at a young age when caries can be prevented more easily. High-risk children can presently be treated with intensified prevention and in the future we will hopefully be able to use immune-supplementation as a way to strengthen their oral immunity," explains Nicklas Strömberg.

Dental costs, including those pertaining to caries treatment, amount to 5 % of global health care-related costs. Caries is the most common cause for failure of fillings and prosthetic replacements. The ability to detect high-risk individuals early could yield large savings for society and individuals both in terms of suffering and costs.

Increased oral pathogens, decreased bacterial diversity predict precancerous stomach cancer lesions

                    

Elevated pathogen colonization and a lack of bacterial diversity in the mouth were identified in people with precancerous lesions that could precede stomach cancer, finds a new study led by New York University College of Dentistry (NYU Dentistry) and New York University School of Medicine.

The findings, published in the November issue of the Journal of Periodontology, provide new evidence that the increase in pathogens associated with periodontal disease - a chronic, destructive disease in the gums and oral cavity - could contribute to the development of precancerous lesions of stomach cancer.

"Our study reinforces earlier findings that poor oral health is associated with an increased risk of precancerous lesions of stomach cancer," said Yihong Li, DDS, MPH, DrPH, professor of basic science and craniofacial biology at NYU Dentistry and the study's corresponding author.

The American Cancer Society estimated that 26,370 new cases of stomach or gastric cancer would be diagnosed in 2016, resulting in 10,703 deaths. Accumulating evidence suggests that chronic inflammation caused by oral bacterial infections may contribute to the development and progression of various types of cancer, including stomach cancer.

Although some risk factors - such as H. pylori colonization, cigarette smoking, and eating salt and preserved foods - have previously been confirmed to contribute to the development of stomach cancer, many new cases unrelated to these risk factors are diagnosed each year. Scientists have hypothesized that a group of pathogens may be responsible for causing periodontal disease and the resulting chronic systemic inflammation that may contribute to the development of gastric cancer.

This study assesses the association between periodontal pathogen colonization and the potential risk of developing precancerous lesions - including chronic atrophic gastritis, intestinal metaplasia, and dysplasia - that may predict stomach cancer.

The researchers studied 105 individuals scheduled to receive an upper endoscopy. After the endoscopic procedure and histopathologic evaluation, 35 people were diagnosed with precancerous lesions of gastric cancer and another 70 people of the same ages without precancerous lesions were included in the study as a control group.

The researchers performed full-mouth examinations to assess participants' periodontal conditions. Saliva and dental plaque samples were collected to evaluate colonization by several of pathogens - P. gingivalis, T. denticola, T. forsythia, and A. actinomycetemcomitans - and to characterize oral microbial diversity.

Compared with the control group, patients with precancerous lesions experienced higher prevalence of bleeding when probed (31.5 percent versus 22.4 percent), higher levels of two pathogens (T. denticola and A. actinomycetemcomitans), and less bacterial diversity in their saliva.

A further analysis, which took into account sociodemographic factors, oral health behaviors, and periodontal assessments, revealed additional predictors of precancerous lesions: elevated colonization of three pathogens (T. forsythia, T. denticola, and A. actinomycetemcomitans), decreased bacterial diversity in dental plaque, and not flossing regularly.

The researchers concluded that the colonization of periodontal pathogens and the alternated bacterial diversity in the oral cavity are important factors that, when at higher or lower levels respectively, may contribute to an increased risk of developing precancerous gastric lesions.

"Based on our findings, treatment for chronic periodontal disease and control of periodontal pathogen infections should be included in future strategies for preventing stomach cancer," said Dr. Li.

Methodologies in orthodontic pain management: A review

                     

Patients experience pain and discomfort during active orthodontic treatment with fixed appliances. It can vary from person to person and is influenced by certain factors such as age, gender, previous pain experiences, stress or anxiety, and type of appliance.

The objective of this literature review was to discuss conventional versus recently introduced treatment modalities used in pain management for orthodontic patients.

According to the reviewed articles, both pharmacological and non-pharmacological methods were introduced in orthodontic pain management. However, orthodontists must use their best professional judgment to assess each case individually and select an appropriate treatment modality based on pain threshold level of an individual.

Research Key Points

• Effective orthodontist-patient communication and targeted nutritional guidance may help in preventing pain and discomfort experienced by the patients to some extent.
• However, based on the available literature, analgesics remained the effective and routine methodology of pain management.
• Some clinicians supported that NSAIDs such as Ibuprofen had no impact on tooth movements as they were administered in lower doses and for a shorter duration. Hence, Ibuprofen was considered a safe and effective drug compared to other NSAIDs. On the contrary, other authors declared a delay in orthodontic tooth movements as a result of NSAID intake.
• Another investigation supported that paracetamol (acetaminophen) was considered the safest NSAID that had no influence on the range of tooth movements as well as root resorption. However, much of what has been published on this subject is still controversial.
• Moreover, while prescribing analgesics, orthodontists must be aware of the pharmacological action as well as the pros and cons related to each drug.
• Nevertheless, pain management is a complex phenomenon. Therefore, further investigations combining different methods of orthodontic pain control with appropriate study designs and large sample sizes are required to improve the quality of evidence.

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For more information about the article, please visit https://benthamopen.com/ABSTRACT/TODENTJ-11-492

• Reference: Hussain AS, et al. Methodologies in Orthodontic Pain Management: A Review. The Open Dentistry Journal, 2017, Vol 11, DOI: 10.2174/1874210601711010492

Tooth cavities can be fought 'naturally'

A new discovery may one day lead to natural anti­cavity products, researchers report.

The scientists from West China School of Stomatology and Academic Centre for Dentistry Amsterdam have figured out the main active ingredient of Galla Chinensis, a natural herb, and further improved its anti-caries efficacy. The finding is published in The Open Dentistry Journal.

To maintain a healthy mouth, the oral environment must be relatively neutral. When the environment in the mouth becomes more acidic, dental cavities or other disorders may develop. Galla Chinensis was revealed to inhibit the acid production of caries-associated bacteria as well as make teeth more resistant to acidic attack.

The research team of West China School of Stomatology has tested hundreds of Chinese herbs and identified that Galla Chinensis has a strong potential to prevent dental caries due to its antibacterial capacity and tooth mineralization benefit. Galla Chinensis also possesses substantial antiviral, anticancer, hepatoprotective, antidiarrheal and antioxidant activities. However, the main active ingredient of Galla Chinensis is unknown, which restricts the application in dentistry.

In the present study, several Galla Chinensis extracts with different main ingredients were obtained and determined by liquid chromatography-mass spectrometry (LC-MS) analysis. The antibacterial capacity was determined using the polymicrobial biofilms model, which can generate reproducible plaque-like biofilms that occur in vivo. The effect of inhibiting tooth demineralization was tested using an in vitro pH-cycling regime, which mimicked the periodic pH change in mouth.

"Medium molecular weight gallotannins are the most active constituent in terms of caries prevention" concluded Xuelian Huang, PhD, DDS, the lead author.

In dental caries, significant reductions in caries prevalence and incidence have been made by the introduction of fluoride. It is not a total cure, however, and there is still a need to seek products complementary to fluoride. With these new findings, the research team is working with the industry to develop new oral care products.

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For more information about the article, please visit https://benthamopen.com/ABSTRACT/TODENTJ-11-447
Reference: Zhou X, et al. Comparison of Composition and Anticaries Effect of Galla Chinensis Extracts with Different Isolation Methods. The Open Dentistry Journal, 2017, Vol 11, DOI: 10.2174/1874210601711010447

Naturally occurring molecule may help prevent and treat atherosclerosis and gum disease

                    

Resolvin E1, a molecule produced naturally in the body from an omega -3 fish oil, topically applied on gum tissues not only prevents and treats gum disease as previously shown (Hasturk et al 2006 and 2007), but also decreases the likelihood for advanced arterial atherosclerotic plaques to rupture and form a dangerous thrombus or blood clot.

The findings, which appear in the journal Current Atherosclerosis Reports, could lead to effective preventive and therapeutic treatments in people with heart disease and/or gum disease without unwanted side effects.

Inflammation is a key pathology of atherosclerosis and may be a major driving force for heart attacks and stroke. There is increasing evidence from numerous research groups that chronic inflammatory diseases including, diabetes, heart disease, rheumatoid arthritis, colitis, pulmonary and kidney diseases, cancer and Alzheimer's disease can benefit by the use of the pro-resolving lipid mediators, resolvins and lipoxins.

To test the effectiveness of lipid mediators on advanced atherosclerosis, researchers from Boston University School of Medicine (BUSM) and The Forsyth Institute used two groups of an experimental model that possessed highly inflamed advanced atherosclerosis.

The first group was treated with a solution applied on gum tissues that contained Resolvin E1 while the second group was treated with salt water as a control.

The group treated with the inflammation-lowering lipid mediator (Resolvin E1) had minimal atherosclerosis and reduced plaque rupture in their aortic artery, while atherosclerosis advanced to more severe form of the disease in the control (salt water) group.

"Current therapies for advanced atherosclerosis are inadequate and often carry high risks, and the Resolvin E1 therapy could provide a very effective and safe therapy that can be taken daily, which would also serve as a preventive approach for plaque inflammation and acute clinical events of heart attack and stroke," explained corresponding author James A. Hamilton, PhD, professor of physiology and biophysics and research professor of medicine at BUSM.

The researchers believe these findings support a paradigm shift in the treatment of both localized and systematic inflammatory conditions that are increasingly prevalent in type 2 diabetes and obesity and may be applicable to other chronic inflammatory diseases.

Treating gum disease may help lower blood pressure

                     

Treatment for gum disease, or periodontitis, significantly lowered blood pressure among Chinese patients at risk for developing high blood pressure, according to preliminary research presented at the American Heart Association's Scientific Sessions 2017, a premier global exchange of the latest advances in cardiovascular science for researchers and clinicians.

This small study compared blood pressure levels after standard and intensive treatment for gum disease. The standard treatment included basic oral hygiene instructions and teeth cleaning with plaque removal above the gum line. The intensive treatment included the standard treatment along with cleaning down to the roots with local anesthesia, antibiotic treatment and dental extractions, if necessary.

Researchers found:

• One month after treatment, systolic blood pressure was nearly 3 points lower in participants receiving intensive treatment, but no significant difference was observed in diastolic blood pressure.
• Three months after treatment, systolic blood pressure was nearly 8 points lower and diastolic pressure was nearly 4 points lower in patients receiving intensive treatment.
• Six months after treatment, systolic blood pressure was nearly 13 points and diastolic blood pressure was almost 10 points lower in patients receiving intensive treatment.

"The present study demonstrates for the first time that intensive periodontal intervention alone can reduce blood pressure levels, inhibit inflammation and improve endothelial function," said study lead author Jun Tao, M.D., Ph.D., chief of the department of Hypertension and Vascular Disease and director of the Institute of Geriatrics Research at The First Affiliated Hospital of Sun Yat-sen University in Guangzhou, China.

Study participants included 107 Chinese women and men age 18 years and over with prehypertension and moderate to severe gum disease. Through random assignment, half of the participants received standard treatment and half received intensive treatment for gum disease.

Researchers noted additional research with patients from diverse backgrounds is needed.
In the United States, high blood pressure affects 29.1 percent of adults aged 18 and over in 2011 - 2012. High blood pressure is a major risk factor for heart and blood vessel disease. Fortunately, most people can manage the disease through diet and lifestyle changes, such as quitting smoking, maintaining a healthy weight, being physically active, limiting alcohol and taking prescribed medications properly.

A focus on dental health can protect children from developing overweight

                    

Talking about dental health with children and parents - about what is healthy and unhealthy for your teeth - can be one way to prevent children from developing overweight. This is suggested in a thesis from Sahlgrenska Academy, Sweden, on children's diet, BMI and well-being.
"Weight can be a sensitive subject, but if you talk about eating behaviors alongside dental health, you're looking at the issue from a different angle," confirms Louise Arvidsson, registered dietitian and PhD student at the Institute of Medicine.
In one of her sub-studies, she reviewed eating behavior, BMI and dental health of 271 pre-school and primary school children in Sweden. The children's height, weight, and food intake over one day were compared with the prevalence of cariogenic microorganisms in saliva - and the link was clear: The children who had higher amount of caries bacteria also had significantly higher BMI and worse eating habits. They ate more frequently and consumed more foods rich in sugar.
"There is absolutely a possibility to catch these children and talk about food habits, specifically in Sweden where the dentists meets with them at an early age, but this needs a good level of collaboration between the general dentistry, the child health care and schools," says Louise Arvidsson.
With good food comes increased self-esteem, better relationships with friends and fewer emotional problems, Louise confirms in a different sub-study. Children that to a higher extent followed general dietary recommendations - wholegrain products, 400-500 grams of fruit and vegetables per day, fish two to three times a week and a low intake of sugar and saturated fat - reported better mental well-being.
The effects were achieved regardless of socio-economic background, and regardless of the children's weight. Her research further shows that good self-esteem could be linked to the healthier eating habits, two years later. A healthy diet and mental well-being might therefore be considered to interact, in a positive spiral.
"We know that adults with depression feel better if, in addition to other treatment, they also meet with a dietitian. The question is whether a healthy diet can have effect also in young children. There has been a lot of focus on physical activity and mental health in children, but diet is an increasingly recognized aspect," says Louise Arvidsson.
The entire thesis is based on data from a large European study, Idefics (with the University of Gothenburg having primary responsibility for Sweden's participation), the aim of which is to document and prevent childhood obesity.
In her thesis, Louise has also highlighted what does not work in protecting children from becoming overweight. Children between the age of 2-10 who were stopped from eating by their parents were generally overweight 5-6 years later.
"It clearly doesn't work, stopping your child from eating too much, or putting them on a diet, as some people were convinced. You really have to look at other methods to control a child's eating habits," says Arvidsson.
"Are you offering carrots as snacks, or both carrots and biscuits? What you eat at home is a very important question, and that you yourself try to make healthy choices. Children do as we do, not as we say."

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Title: Diets of European children, with focus on BMI, well-being, and families

Dental X-rays reveal Vitamin D deficiency

Human teeth hold vital information about Vitamin D deficiency, a serious but often hidden condition that can now be identified by a simple dental X-ray, McMaster anthropologists Lori D'Ortenzio and Megan Brickley have found.

Their research appears today in the International Journal of Paleopathology.

The researchers and their colleagues had previously discovered that human teeth hold a detailed and permanent record of serious Vitamin D deficiency, or rickets. That record takes the form of microscopic deformities in dentin, the material that makes up the mass of the tooth, and can be extremely valuable for understanding precisely when people, even those who lived centuries ago, were deprived of sunlight, the main source of Vitamin D.

The record is preserved by enamel, which protects teeth from breaking down, unlike bones, which are subject to decay.

The problem with looking for such deformities is that a tooth must be cut open to read the patterns that form a lifetime's Vitamin D record, and the supply of post-mortem teeth available for study is limited.

To avoid wasting precious specimens, the researchers went looking for a way to isolate teeth for further study. By using X-rays to study the readily observable shapes of the "pulp horns" -- the dark shadow at the centre of the image of a tooth -- they found a consistent, recognizable pattern that could prove helpful not only to their studies of archaeological teeth, but to living people who may not realize they are suffering from Vitamin D deficiency.

"We were looking for a non-destructive method so we wouldn't need to destroy precious archaeological material to see if there had been a deficiency," says D'Ortenzio, a PhD candidate in anthropology and lead author of the paper. "Now we know which teeth to look at."

The pulp shape in a healthy person's tooth resembles an arch topped by two cat ears, while the pulp shape of a person who has had a severe deficiency of Vitamin D is asymmetrical and constricted, and typically looks like the profile of a hard-backed chair.

D'Ortenzio and Brickley's previous research had suggested such a recognizable pattern, and their examination of both historic and current teeth proved that X-ray images are consistent and reliable indicators of prior deficiency.

"It was a real Eureka! It wasn't just that it looked different. It was different," says Brickley, a Professor of Anthropology who holds the Canada Research Chair in the Bioarchaeology of Human Disease. "I think it's really important. It was a piece of work that aimed to look more at past individuals, but it has the potential to contribute to modern health care as well."

Since the consequences of Vitamin D deficiency can be severe - especially in terms of bone health - knowing who has had a deficiency can help identify people who may have ongoing issues in time to prevent worse damage, the researchers say. If regular dental X-rays show a problem, blood tests can confirm whether there is an ongoing deficiency.

Such evidence could be particularly valuable in the case of children whose bones are still growing, the researchers say, and spotting a problem early could head off future problems with Vitamin-D related bone deficiency.

Knowing more about ongoing Vitamin D deficiency can also help to determine what is the best balance between protecting people from harmful UV rays and making sure they get enough sun to maintain a healthy level of the vital nutrient.

Dental filling failure linked to smoking, drinking and genetics

                     

New research shows that people who drink alcohol or men who smoke are more likely to suffer a failed dental filling. Strikingly, the research team also found that a genetic difference in some patients is associated with increased filling failure rates. The study, published today in open-access journal Frontiers in Medicine, also shows no major difference in filling failure rates between traditional amalgam and newer composite resin fillings. The results suggest that genetic analysis might help dentists to personalize treatments for their patients, which could lead to improved outcomes.

Fillings can fail for a variety of reasons, including reemergence of the initial tooth decay or the filling becoming detached. Until now, the jury has been out on whether newer composite resin fillings are as durable as traditional amalgam fillings, which have been in use for more than 150 years but which contain mercury, a toxic metal.

To investigate this, researchers from America and Brazil accessed a large repository of dental records from a dental school in Pittsburgh, which contained information on patient fillings and rates of failure up to five years after the filling procedure.

The researchers found that overall, there were no major differences between patients receiving amalgam or composite fillings in terms of filling failure rates. This suggests that composite fillings are at least as durable as amalgam fillings, and offer a viable alternative with no toxic ingredients.

The repository also contained information about patient lifestyles, including smoking and drinking habits, and a DNA sample from each patient -- allowing the team to investigate whether patient lifestyle and genetic factors could affect the failure rate of composite fillings.

The team found that within two years of the procedure, fillings failed more often in patients who drank alcohol, and the overall filling failure rate was higher in men who smoked. Furthermore, a difference in the gene for matrix metalloproteinase (MMP2), an enzyme found in teeth, was linked to increased filling failure.

The researchers hypothesize that MMP2 might be able to degrade the bond between the filling and the tooth surface, potentially leading to failure. While this link and preliminary hypothesis are intriguing, the researchers have not yet confirmed whether differences in the MMP2 gene are responsible for failed fillings, and will need to investigate this further. However, the results suggest that personal factors for each patient appear to influence their chance of filling failure, rather than the filling material their dentist used.

"A better understanding of individual susceptibility to dental disease and variation in treatment outcomes will allow the dental field to move forward," says Alexandre Vieira, a researcher involved in the study. "In the future, genetic information may be used to personalize dental treatments and enhance treatment outcomes."

Half of UK adults miss a quarter of their teeth when brushing

                     

Thorough tooth brushing is recognised as the foundation of good oral health regimes, and an effective way to avoid tooth decay and gum disease.
Yet a new study into the UK's tooth brushing habits released today (Wednesday 1st November 2017) reveals a disturbing trend of poor oral hygiene habits that are a major contributor to the UK's £3.4bn-plus annual bill for NHS dental treatments, and for private patients. Each week, more than 1 million patients in the UK use NHS dental services - many of them seeking treatment for dental disease, the consequences of which costs the NHS a huge £3.4bn a year.
The study, commissioned by a consortium of dentists behind Brushlink - the first smartphone 'tooth brushing tracker' that works with any toothbrush and which launches today - found that half of UK adults (48%) admit that they 'orphan' at least a quarter of the teeth in their mouth by consistently missing them when they brush.
Tooth brushing efficiency is even lower among the Millennial generation (aged 18- 34) where less than a third (29%) reach all of their teeth each time they brush compared with over half (55%) for those aged 55 and over.
In another worrying flag for the UK's oral health, the study also found that six in ten (61%) adults have never been shown how to brush their teeth correctly by a dentist or hygienist. This fact could explain why a quarter (24%) of UK adults say that someone in their household has had dental treatment in the last two years for problems they think could have been prevented by better tooth brushing and oral hygiene.
Problems like those highlighted by the report (See full results tables over) were one of the reasons why award-winning dentist Dr Dev Patel invented Brushlink - a dental coaching device and app in 2015. The device is the first that can track and coach people on brushing frequency, duration and angles while making this data available to dentists if consented - and it works with any toothbrush, manual or electric.
Brushlink has also been built to provide a brushing score each time it is used. This is displayed along with 'in-brush' coaching tips and hints via a Bluetooth connection to a smartphone app; however, it also stores data for up to three months in case the user does not have a phone in the bathroom.
Dr Dev Patel, Founder and CEO of Brushlink said:
"As a practising dentist, I have always been shocked by the lack of feedback between patient and dentist. We have always had to rely on what we see inside the mouth ever six months rather than having any reliable data about how people are brushing. I invented Brushlink to plug this gap by providing coaching to patients but also accurate monitoring of everything they are doing with their toothbrush between dentist visits."
Professor Elizabeth Kay MBE, Foundation Dean Peninsula Dental School, Oral Health Topic Expert for NICE and a Brushlink Scientific Committee member, commented:
"This survey has revealed some intriguing insights into our oral health regimes and patients' relationships with the dental health professionals who care for them. There is no substitute for good tooth brushing practices when it comes to maintaining a healthy mouth, yet it would appear from the survey that there is a lot more that we can all do to achieve this effectively.
She added: "The fact that this survey is in association with the launch of a new dental care product - and one which I think is the most amazing oral health product that I have seen in a long time - should encourage people to takes its findings seriously, as it has been commissioned by a group of dentists who are passionate about improving the oral health of the nation."

Why gum disease is associated with atherosclerosis

Heart disease and fatty clogs in the arteries go hand in hand. But new evidence suggests the fatty molecules might come not only from what you eat, but from the bacteria in your mouth, report UConn scientists in the 16 August issue of the Journal of Lipid Research. The research may explain why gum disease is associated with heart trouble.

Heart attacks and strokes are the crises we notice, but they result from a slow process of atherosclerosis, the hardening and clogging of the arteries with fatty substances called lipids. Immune cells stick to the walls of blood vessels, scavenge lipids, and multiply. The blood vessel walls inflame and thicken as the smooth muscle cells lining them change, swelling and dividing to create plaques, clogs, and warty growths called atheromas.

For a very long time, doctors and researchers assumed that the lipids came from eating fatty, cholesterol-rich food. But the research hasn't borne this out; some people who eat large amounts of the foods we thought were the sources of the fat, such as eggs, butter, fatty fish, and meat, don't necessarily develop heart disease.

UConn researchers believe they may have solved part of the puzzle. Using careful chemical analysis of atheromas collected from patients by a colleague at Hartford Hospital, they found lipids with a chemical signature unlike those from animals at all. Instead, these strange lipids come from a specific family of bacteria.

"I always call them greasy bugs because they make so much lipid. They are constantly shedding tiny blebs of lipids. Looks like bunches of grapes," on a bacterial scale, says Frank Nichols, a UConn Health periodontist who studies the link between gum disease and atherosclerosis. The bacteria, called Bacteroidetes, make distinctive fats. The molecules have unusual fatty acids with branched chains and odd numbers of carbons (mammals typically don't make either branched chain fatty acids or fatty acids with odd numbers of carbons).

Xudong Yao, a UConn associate professor of chemistry who analyzed the lipid samples, says the chemical differences between bacterial and human lipids result in subtle weight differences between the molecules. "We used these weight differences and modern mass spectrometers to selectively measure the quantity of the bacterial lipids in human samples to link the lipids to atherosclerosis," he says. "Establishment of such a link is a first step to mark the lipids as indicators for early disease diagnosis."

The marked chemical differences between Bacteroidetes lipids and the human body's native lipids may be the reason they cause disease, suggests Nichols. The immune cells that initially stick to the blood vessel walls and collect the lipids recognize them as foreign. These immune cells react to the lipids and set off alarm bells.

Nichols and Yao's team also showed that despite being non-native lipids, the Bacteroidetes lipids could be broken down by an enzyme in the body that processes lipids into the starting material to make inflammation-enhancing molecules. So the Bacteroidetes lipids have a double whammy on the blood vessels: the immune system sees them as a signal of bacterial invasion, and then enzymes break them down and super-charge the inflammation.

Despite the havoc they wreak, it's not the Bacteroidetes bacteria themselves invading. Usually these bacteria stay happily in the mouth and gastrointestinal tract. If conditions are right, they can cause gum disease in the mouth, but not infect the blood vessels. But the lipids they produce pass easily through cell walls and into the bloodstream.

The next step in the research is to analyze thin slices of atheroma to localize exactly where the bacterial lipids are accumulating. If they can show the Bacteroidetes-specific lipids are accumulating within the atheroma, but not in the normal artery wall, that would be convincing evidence that these unusual lipids are associated specifically with atheroma formation, and therefore contribute to heart disease.