Salivary mucins play active role to fight cavities

		IMAGE: The viscoelastic properties of mucus and saliva are attributed to mucins, large glycoproteins that play a key role in host defense and maintaining a healthy microbiome. Human salivary mucins protect... Click here for more information.

Salivary mucins, key components of mucus, actively protect the teeth from the cariogenic bacterium, Streptococcus mutans, according to research published ahead of print in Applied and Environmental Microbiology. The research suggests that bolstering native defenses might be a better way to fight dental caries than relying on exogenous materials, such as sealants and fluoride treatment, says first author Erica Shapiro Frenkel, of Harvard University, Cambridge, MA.

S. mutans attaches to teeth using sticky polymers that it produces, eventually forming a biofilm, a protected surface-associated bacterial community that is encased in secreted materials, says Frenkel. As S. mutans grows in the biofilm, it produces organic acids as metabolic byproducts that dissolve tooth enamel, which is the direct cause of cavities. "We focused on the effect of the salivary mucin, MUC5B on S. mutansattachment and biofilm formation because these are two key steps necessary for cavities to form," says Frenkel.

		IMAGE: This is two overlayed fluorescent microscopy images ofStreptococcus mutans, the primary bacteria responsible for dental cavities. When S. mutans forms biofilms on the tooth surface, it produces organic acids... Click here for more information.

"We found that salivary mucins don't alterS. mutans' growth or lead to bacterial killing over 24 hours," says Frenkel. "Instead, they limit biofilm formation by keeping S. mutans suspended in the liquid medium. This is particularly significant forS. mutans because it only causes cavities when it is attached, or in a biofilm on the tooth's surface." She adds that the oral microbiome is better preserved when naturally occurring species aren't killed. "The ideal situation is to simply attenuate bacterial virulence," she says.

The study grew out of previous work in the investigators' laboratory showing that other types of mucins, such as porcine gastric mucins, had protective effects against common lung pathogens, says Frenkel. With this in mind, they suspected that salivary mucins would play a protective role, but they were not sure what that would be.

		IMAGE: This is a fluorescent microscopy image of a Streptococcus mutans biofilm. Click here for more information.

"Defects in mucin production have been linked to common diseases such as asthma, cystic fibrosis, and ulcerative colitis," says Frenkel. "There is increasing evidence that mucins aren't just part of the mucus for structure or physical protection, but that they play an active role in protecting the host from pathogens and maintaining a healthy microbial environment. We wanted to apply these emerging ideas to a disease model that is a widespread, global public health problem--cavities. We chose to study the interaction of MUC5B with Streptococcus mutans because it is the primary cavity-causing bacteria in the oral cavity."

The research makes a fundamental contribution to scientific understanding of host-microbe interactions, says principal investigator Katharina Ribbeck, of the Massachusetts Institute of Technology, Cambridge MA. "It is generating a paradigm shift from the textbook view of mucus as a simple catchall filter for particles, towards the understanding that mucus is a sophisticated bioactive material with powerful abilities to manipulate microbial behavior."

Sleeping in dentures doubles the risk of pneumonia in the elderly

Poor oral health and hygiene are increasingly recognized as major risk factors for pneumonia among the elderly. To identify modifiable oral health-related risk factors, lead researcher Toshimitsu Iinuma, Nihon University School of Dentistry, Japan, and a team of researchers prospectively investigated associations between a constellation of oral health behaviors and incidences of pneumonia in the community-living of elders 85 years of age or older. This study, titled "Denture Wearing During Sleep Doubles the Risk of Pneumonia in Very Elderly," has been published by the International and American Associations for Dental Research (IADR/AADR in the OnlineFirst portion of the Journal of Dental Research (JDR)

At baseline, 524 randomly selected seniors (228 males, 296 females, average age was 87.8 years old) were examined for oral health status and oral hygiene behaviors as well as medical assessment, including blood chemistry analysis, and followed up annually until first hospitalization for or death from pneumonia. Over a three-year follow-up period, 48 events associated with pneumonia were identified (20 deaths and 28 acute hospitalizations). Among 453 denture wearers, 186 (40.8%) who wore their dentures during sleep, were at higher risk for pneumonia than those who removed their dentures at night.

In a multivariate Cox model, both perceived swallowing difficulties and overnight denture wearing were independently associated with approximately 2.3-fold higher risk of the incidence of pneumonia, which was comparable with the high risk attributable to cognitive impairment, history of stroke and respiratory disease. In addition, those who wore dentures while sleeping were more likely to have tongue and denture plaque, gum inflammation, positive culture for Candida albicans, and higher levels of circulating interleukin-6 as compared to their counterparts.

This study provides empirical evidence that denture wearing during sleep is associated not only with oral inflammatory and microbial burden but also with incident pneumonia, suggesting potential implications of oral hygiene programs for pneumonia prevention in the community. Frauke Mueller, University of Geneva, Switzerland, wrote a perspective titled "Oral Hygiene Reduces the Mortality From Aspiration Pneumonia in Frail Elders," commenting that these findings lead to a simple and straight forward clinical recommendation—denture wearing during the night should be discouraged in geriatric patients.

Widely used depression drug associated with dental implant failure

The International and American Associations for Dental Research (IADR/AADR) have published a paper titled "SSRIs and the Risk of Osseointegrated Implant Failure – A Cohort Study." Selective Serotonin Reuptake Inhibitors (SSRIs), the most widely used drugs for the treatment of depression, have been reported to reduce bone formation and increase the risk of bone fracture. Since osseointegration is influenced by bone metabolism, this study investigates the association between SSRIs and the risk of failures in osseointegrated implants. The manuscript, by researchers Khadijeh Al-Abedalla, Samer Abi Nader, Belinda Nicolau, Emad Rastikerdar, Faleh Tamimi and Xixi Wu, from McGill University, Montreal, Quebec, Canada; and Nach Daniel, from East Coast Oral Surgery, Moncton, New Brunswick, Canada, is published in the OnlineFirst portion of the IADR/AADR Journal of Dental Research (JDR).

This retrospective cohort study was conducted on patients treated with dental implants from January 2007 to January 2013. A total of 916 dental implants in 490 patients (94 implants on 51 patients using SSRIs) were used to estimate the risk of failure associated with the use of SSRIs. Data analysis involved cox proportional hazards, generalized estimating equations models and Kaplan-Meier analysis. After three to 67 months of follow-up, 38 dental implants failed and 784 succeeded in nonusers group while 10 failed and 84 succeeded in SSRIs-users group.

The primary outcome was that compared with non-users of SSRIs, SSRIs usage was associated with an increased risk of dental implants failure (HR= 2∙31; P< 0∙01). The failure rates were 4.6% for SSRI non-users and 10.6% SSRI users, respectively. The secondary outcomes were that small implant diameters (≤4mm) (P=0∙01), bone augmentation (P=0∙04) and smoking habits (P<0 acquired="" also="" and="" associated="" be="" compliance="" could="" dose="" drug="" failure.="" files="" font="" from="" higher="" implant="" limitation="" main="" not="" of="" patients.="" period="" retrospective="" risk="" seemed="" study="" that="" the="" this="" to="" treatment="" was="" with="">

Within the limits of this study, these findings indicate that treatment with SSRIs is associated with an increased failure risk of osseointegrated implants.

Up to 3,000 times the bacterial growth on hollow-head toothbrushes

Solid-head power toothbrushes retain less bacteria compared to hollow-head toothbrushes, according to researchers at The University of Texas Health Science Center at Houston (UTHealth) School of Dentistry.

The results of the study are published in the August issue of the Journal of Dental Hygiene. Lead author and professor at the UTHealth School of Dentistry, Donna Warren Morris, R.D.H., M.Ed., notes that microbial counts were lower in the solid-head toothbrush group than in the two hollow-head toothbrush groups in 9 out of 10 comparisons.

“Toothbrushes can transmit microorganisms that cause disease and infections. A solid-head design allows for less growth of bacteria and bristles should be soft and made of nylon,” Morris said. “It is also important to disinfect and to let your toothbrush dry between uses. Some power toothbrushes now include an ultraviolet system or you can soak the head in mouthwash for 20 minutes.” 

The study was conducted over a three-week period where participants brushed twice daily with one out of three randomly assigned power toothbrushes. Participants used non-antimicrobial toothpaste and continued their flossing routine throughout the study, but refrained from using other dental products like mouthwash.

“The packaging on most power toothbrushes won’t distinguish between a hollow-head and a solid-head design,” Morris said. “The best way to identify a solid-head design is through the connection to the body of the power toothbrush. Naturally, there will be some space to connect the two parts but a significant portion will be solid, up to the bristles or brush head.”

During the study the brush heads were exposed to five categories of oral microorganisms: anaerobes and facultative microorganisms, yeast and mold, oral streptococci and oral enterococci anaerobes, Porphyromonas gingivalis and Fusobacterium species.

The article also states that there is no present or published study that has demonstrated that bacterial growth on toothbrushes can lead to systematic health effects, but as Morris stated, several microorganisms have been associated with systemic diseases.

“We do know and there are studies that have linked Fusobacterium to colorectal cancer. Some of these other bacteria have been linked with cardiovascular disease,” Morris said. “There is a high association with gum disease and cardiovascular disease. Researchers have been able to culture the same bacteria around the heart that causes gum disease. ”

What's the best way to brush teeth? Even dentists and dental associations don't agree

Advice on how we should brush our teeth from dental associations and toothpaste companies is 'unacceptably inconsistent', finds new UCL research

Advice on how we should brush our teeth from dental associations and toothpaste companies is 'unacceptably inconsistent', finds new UCL (University College London) research.

The study, published in the British Dental Journal, looked at the brushing advice given by dental associations across ten countries, toothpaste and toothbrush companies and in dental textbooks. They found a wide range of recommendations on what brushing method to use, how often to brush and for how long.

The researchers found no clear consensus between the various sources, and a 'worrying' lack of agreement between advice from dental associations compared with dental textbooks.

"The public needs to have sound information on the best method to brush their teeth," says Aubrey Sheiham, Emeritus Professor of Dental Public Health (UCL Epidemiology & Public Health), senior author of the study. "If people hear one thing from a dental association, another from a toothbrush company and something else from their dentist, no wonder they are confused about how to brush. In this study we found an unacceptably inconsistent array of advice from different sources.

"Dental associations need to be consistent about what method to recommend, based on how effective the method is. Most worryingly, the methods recommended by dental associations are not the same as the best ones mentioned in dental textbooks. There is no evidence to suggest that complicated techniques are any better than a simple gentle scrub."

The most commonly-recommended technique involves gently jiggling the brush back and forth in small motions, with the intention of shaking loose any food particles, plaque and bacteria. However, no large-scale studies have ever shown this method to be any more effective than basic scrubbing.

"Brush gently with a simple horizontal scrubbing motion, with the brush at a forty-five degree angle to get to the dental plaque," Professor Sheiham advises. "To avoid brushing too hard, hold the brush with a pencil grip rather than a fist. This simple method is perfectly effective at keeping your gums healthy.

"There is little point in brushing after eating sweets or sugary drinks to prevent tooth decay. It takes bacteria from food about two minutes to start producing acid, so if you brush your teeth a few minutes after eating sugary foods, the acid will have damaged the enamel."

The conflicting messages given by different organisations highlight the need for research into how effective different brushing methods are. At present, the expert advice in the guidelines, 'The scientific basis of dental health education', recommend a simple scrubbing technique as it is easy to learn and there is no evidence to justify a more complicated method.

"The wide range of recommendations we found is likely due to the lack of strong evidence suggesting that one method is conclusively better than another," says lead author Dr John Wainwright, who carried out the study at UCL and is now a practising dentist. "I advise my patients to focus their brushing on areas where plaque is most likely to collect – the biting surfaces and where the teeth and gums meet – and to use a gentle scrubbing motion. All too frequently I am asked why the method I am describing differs from how previous dentists have taught them in the past.

"What I feel we need is better research into what the easiest to learn, most effective and safest way to brush is. The current situation where not just individual dentists, but different dental organisations worldwide are all issuing different brushing guidelines isn't just confusing – it's undermining faith and trust in the profession as a whole. For something most people do twice a day, you would expect dentists to send a clearer, more unified message to their patients on how to brush their teeth."^

Link between periodontitis and atherosclerosis

Chronic oral infection with the periodontal disease pathogen, Porphyromonas gingivalis, not only causes local inflammation of the gums leading to tooth loss but also is associated with an increased risk of atherosclerosis. A study published on July 10th in PLOS Pathogens now reveals how the pathogen evades the immune system to induce inflammation beyond the oral cavity.

Like other gram-negative bacteria, P. gingivalis has an outer layer that consists of sugars and lipids. The mammalian immune system has evolved to recognize parts of this bacterial coating, which then triggers a multi-pronged immune reaction. As part of the "arms race" between pathogens and their hosts, several types of gram-negative bacteria, including P. gingivalis, employ strategies by which they alter their outer coats to avoid the host immune defense.

Caroline Attardo Genco, from Boston University School of Medicine, USA, in collaboration with Richard Darveau, at the University of Washington School of Dentistry, USA, and colleagues focused on the role of a specific lipid expressed on the outer surface of P. gingivalis, called lipid A, which is known to interact with a key regulator of the host's immune system called TLR4. P. gingivalis can produce a number of different lipid A versions, and the researchers wanted to clarify how these modify the immune response and contribute to the ability of the pathogen to survive and cause inflammation—both locally, resulting in oral bone loss, and systemically, in distant blood vessels.

They constructed genetically modified strains of P. gingivalis with two distinct lipid A versions. The resulting bacteria produced either lipid A that activated TLR4 (called "agonist") or lipid A that interacted with TLR4 but blocked activation ("antagonist"). Utilizing these strains, they demonstrate that P. gingivalis production of antagonist lipid A renders the pathogen resistant to host bacterial killing responses. This facilitates bacterial survival in macrophages, specific immune cells that normally not only gobble up the bacteria but also "digest" and kill them.

When the researchers infected atherosclerosis-prone mice with the P. gingivalis TLR4 antagonist strain, they found that this exacerbates inflammation in the blood vessels and promotes atherosclerosis. In contrast, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A variations, which demonstrates that there are distinct mechanisms for induction of local versus systemic inflammation.

The researchers conclude, "P. gingivalis modifies its lipid A structure in order to evade host defenses and establish chronic infection leading to persistent systemic low-grade inflammation". They go on to state that "uniquely among gram-negative pathogens, P. gingivalis evasion of TLR4-mediated host immunity results in progression of inflammation at a site that is distant from local infection by gaining access to the vasculature."