Vaping changes oral microbiome, increasing risk for infection

Using e-cigarettes alters the mouth's microbiome--the community of bacteria and other microorganisms--and makes users more prone to inflammation and infection, finds a new study led by researchers at NYU College of Dentistry.

The study--published in iScience, a Cell Press journal--is the first to demonstrate that vaping changes the oral microbiome and adds to our limited understanding of the safety profile of e-cigarettes.

The mouth is a gateway to the body and harbors many microbial species that colonize our respiratory and digestive tracts. It is well established that smoking traditional cigarettes raises the risk of gum disease and infection by bringing about physiological and structural changes, fostering an environment in which certain infection-causing bacteria flourish and contributing to immune dysfunction.

E-cigarettes--handheld devices in which nicotine is inhaled in a vapor--are thought to be less harmful than cigarettes, but little research (and no long-term data) exist on the safety of e-cigarettes. While vaping has quickly grown in popularity in recent years, a growing number of people are falling ill or dying from vaping-related illnesses.

"Given the popularity of vaping, it is critical that we learn more about the effects of e-cigarette aerosols on the oral microbiome and host inflammatory responses in order to better understand the impact of vaping on human health," said Xin Li, PhD, associate professor of basic science and craniofacial biology at NYU College of Dentistry and the study's co-senior author.

"The oral microbiome is of interest to us because research shows that changes in its microbial community as a result of environmental and host factors contribute to a range of health issues, including cavities, gum disease, halitosis, and medical conditions such as diabetes, cardiovascular disease, and cancers," said Deepak Saxena, PhD, professor of basic science and craniofacial biology at NYU College of Dentistry and the study's co-senior author.

In this study, Li, Saxena, and their colleagues examined e-cigarette vapor and its influence on the oral microbiome and immune health. They also evaluated how vaping influences infection efficiency of oral pathogens in cell lines using a novel e-cigarette aerosol generating machine and measured pro-inflammatory immune mediators.

Through oral exams and saliva samples, the researchers studied the oral microbiome of 119 human participants from three groups: e-cigarette users, regular cigarette smokers, and those who had never smoked. Gum disease or infection was significantly higher among cigarette smokers (72.5 percent), followed by e-cigarette users (42.5 percent) and non-smokers (28.2 percent).

Using 16S rRNA high throughput sequencing, a technique used to profile microbial communities, the researchers observed different microorganisms in the saliva of e-cigarette users, cigarette smokers, and non-smokers. For instance, e-cigarette users had an abundance of Porphyromonas bacteria, while an increase in Veillonella bacteria was found in both e-cigarette and cigarette users.

"The predominance of these periodontal pathogens in the mouths of e-cigarette users and traditional smokers is a reflection of compromised periodontal health," said Li.

The researchers also found that the altered microbiome in e-cigarette users influenced the local host immune environment compared to non-smokers and cigarette smokers. IL-6 and IL1β--cytokines involved in inflammatory responses--were highly elevated in e-cigarette users. Cell studies also showed upregulation of IL-6 after exposure to e-cigarette aerosols, resulting in an elevated inflammatory response. Moreover, e-cigarette aerosols made cells prone to bacterial infection, which points to a greater risk for infection in e-cigarette users.

"Our study suggests that vaping electronic cigarettes causes shifts in the oral environment and highly influences the colonization of complex microbial biofilms, which raises the risk for oral inflammation and infection," said Saxena.

Study: Patients commonly prescribed opioids and antibiotics for dental conditions at EDs

A study in the March issue of The Journal of the American Dental Association from the Centers for Disease Control and Prevention found that antibiotics and opioids are frequently prescribed during emergency department visits for dental conditions, further emphasizing the need for continued efforts to combat both opioid abuse and overuse of antibiotics.

The authors found that more than 50 percent of patients who visited the emergency department for a dental-related condition filled a prescription for antibiotics and approximately 40 percent filled a prescription for opioids, based on data from 2012-2014. Further, the authors found that more than 30 percent of patients filled prescriptions for both an antibiotic and an opioid as a result of their visit.

"Given previous findings that dental-related diagnoses are a common and potentially avoidable reason for [emergency department] visits, the prescribing of antibiotics and opioids for these conditions becomes even more concerning," wrote the study authors.

In 2019, as part of its longstanding antibiotic stewardship efforts, the American Dental Association (ADA) released a new guideline indicating that, in most cases, antibiotics are not recommended for toothaches, which are a common dental-related reason to visit an emergency department. The guideline was developed by a multidisciplinary panel, including an emergency medicine physician nominated by the American College of Emergency Physicians.

The ADA has also held a longstanding commitment to raising awareness and taking action on the opioid public health crisis. Since 2011, the ADA has advocated to keep opioid pain relievers from harming dental patients and their families and worked to raise professional awareness on medication alternatives to opioids. A growing body of research supports ADA policy that dentists should consider prescribing non-steroidal anti-inflammatory drugs (NSAIDs) alone or in combination with acetaminophen over opioids as first-line therapy for acute pain management. In March 2018, the organization adopted policy that indicates a combination of ibuprofen and acetaminophen can be just as effective as opioids for acute pain.

Study reveals how too much fluoride causes defects in tooth enamel

Changes within enamel cells point to mechanism by which excessive fluoride leads to fluorosis

NEW YORK UNIVERSITY

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VIDEO: DENTAL FLUOROSIS IS A CONDITION CAUSED BY OVEREXPOSURE TO FLUORIDE DURING CHILDHOOD. NYU COLLEGE OF DENTISTRY'S RODRIGO LACRUZ EXPLAINS HOW EXPOSING TEETH TO EXCESSIVE FLUORIDE ALTERS CALCIUM SIGNALING, MITOCHONDRIAL FUNCTION,... view more 

CREDIT: KATE LORD / NEW YORK UNIVERSITY

Exposing teeth to excessive fluoride alters calcium signaling, mitochondrial function, and gene expression in the cells forming tooth enamel--a novel explanation for how dental fluorosis, a condition caused by overexposure to fluoride during childhood, arises. The study, led by researchers at NYU College of Dentistry, is published in Science Signaling.

Fluoride is a naturally occurring mineral that helps to prevent cavities by promoting mineralization and making tooth enamel more resistant to acid. It is added to drinking water around the world--the U.S. Department of Health and Human Services recommends a level of 0.7 parts per million--and all toothpastes backed by the American Dental Association's Seal of Acceptance contain fluoride. The Centers for Disease Control and Prevention (CDC) named water fluoridation one of 10 great public health achievements of the 20th century for its role in reducing tooth decay.

While low levels of fluoride help strengthen and protect tooth enamel, too much fluoride can cause dental fluorosis--a discoloration of teeth, usually with opaque white marks, lines, or mottled enamel and poor mineralization. Dental fluorosis occurs when children between birth and around nine years of age are exposed to high levels fluoride during this critical window when their teeth are forming, and can actually increase their risk of tooth decay. A survey by the CDC found that roughly 25 percent of the U.S. population examined (ages 6 to 49) show some degree of dental fluorosis.

"The benefits of fluoride for oral health considerably outweigh the risks. But given how common dental fluorosis is and how poorly understood the cellular mechanisms responsible for this disease are, it is important to study this problem," said Rodrigo Lacruz, PhD, associate professor of basic science and craniofacial biology at NYU College of Dentistry and the study's senior author.

To investigate the molecular bases of dental fluorosis, the researchers analyzed the effects of exposing tooth enamel cells to fluoride--levels on the higher end of what you would find in drinking water and consistent with what is found in areas where people commonly have fluorosis. They then assessed fluoride's impact on calcium signaling within the cells, given calcium's role in mineralizing tooth enamel.

The researchers found that exposing enamel cells from rodents to fluoride resulted in calcium dysregulation, with decreases in calcium entering and stored in the endoplasmic reticulum, a compartment within cells with many functions, including storing calcium. In addition, fluoride disrupted the function of mitochondria (the cells' power generators), and therefore energy production was altered. Finally, RNA sequencing--which queries the genomes of cells--revealed that, in enamel cells exposed to fluoride, there was an increased expression of genes encoding endoplasmic reticulum stress response proteins and those encoding mitochondrial proteins, which are involved in producing the cell's energy.

"This gives us a very promising mechanistic view of how fluorosis arises," Lacruz said. "If your cells have to make enamel, which is heavily calcified, and due to exposure to too much fluoride the cells undergo continued stress in their capacity to handle calcium, that will be reflected in the enamel crystals as they are formed and will impact mineralization."

The researchers then repeated the experiment using early-stage kidney cells from humans, but they did not observe the same effects when the kidney cells were exposed to fluoride--suggesting that enamel cells are different from cells forming tissue in other parts of the body.

"You would think that if you expose the enamel cells and kidney cells to the same stressor--treating them with the same amount of fluoride for the same period of time--that you'd have more or less similar responses. But that was not the case," said Lacruz. "Under the same circumstances, enamel cells react to coping with stress in vastly different ways than kidney cells. We are unraveling a mechanism that highlights the uniqueness of enamel cells and explains why fluorosis is more of a problem in the teeth than anywhere else in the body."

Gum disease, inflammation, hardened arteries may be linked to stroke risk

Gum disease was associated with a higher rate of strokes caused by hardening of large arteries in the brain and also with severe artery blockages that haven't yet caused symptoms, according to preliminary research to be presented at the American Stroke Association's International Stroke Conference 2020 - Feb. 19-21 in Los Angeles, a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

Two studies raise the possibility that treating gum disease alongside other stroke risk factors might reduce the severity of artery plaque buildup and narrowing of brain blood vessels that can lead to a new or a recurrent stroke. However, these two studies could not conclusively confirm a cause-and-effect relationship between gum disease and artery blockage or stroke risk.

"Gum disease is a chronic bacterial infection that affects the soft and hard structures supporting the teeth and is associated with inflammation. Because inflammation appears to play a major role in the development and worsening of atherosclerosis, or 'hardening' of blood vessels, we investigated if gum disease is associated with blockages in brain vessels and strokes caused by atherosclerosis of the brain vessels," said Souvik Sen, M.D., M.S., M.P.H., author of both studies and professor and chair of the Department of Neurology at the University of South Carolina School of Medicine in Columbia.

Periodontal disease association with large artery atherothrombotic stroke (Oral Presentation 85)

Researchers examined 265 patients (average age of 64; 49% white; 56% male) who experienced a stroke between 2015 and 2017, analyzing whether gum disease was associated with specific types of stroke.

They found:

• Large artery strokes due to intracranial atherosclerosis were twice as common in patients with gum disease as in those without gum disease;
• Patients with gum disease were three times as likely to have a stroke involving blood vessels in the back of the brain, which controls vision, coordination and other vital bodily functions; and
• Gum disease was more common in patients who had a stroke involving large blood vessels within the brain, yet not more common among those who had a stroke due to blockage in blood vessels outside the skull.

Role of periodontal disease on intracranial atherosclerosis (Oral Presentation 136)

In 1,145 people who had not experienced a stroke, selected from the Dental Atherosclerosis Risk in Communities (DARIC) Study, researchers used two magnetic resonance images to measure blockages in arteries inside the brain. Participants were an average age of 76; 78% were white, and 55% were female. Periodontal examinations were used to classify the presence and severity of gum disease.

Researchers found:

• Arteries in the brain were severely blocked (50% or more) in 10% of participants;
• People with gingivitis, inflammation of the gums, were twice as likely to have moderately severe narrowed brain arteries from plaque buildup compared to those with no gum disease; and
• After adjusting for risk factors such as age, high blood pressure and high cholesterol, people with gingivitis were 2.4 times as likely to have severely blocked brain arteries.

"It's important for clinicians to recognize that gum disease is an important source of inflammation for their patients and to work with patients to address gum disease," Sen said

The study excluded people who had gum disease serious enough to have resulted in tooth loss.

"We are working on a current study to evaluate if treatment of gum disease can reduce its association with stroke," Sen said.

Cleaner Teeth, Healthier Heart?

Brushing your teeth may be good for your heart, a new study suggests.

It included more than 161,000 South Korean adults, ages 40 to 79, with no history of heart failure or the heart rhythm disorder atrial fibrillation.

Between 2003 and 2004, participants had a routine medical exam and were asked about a wide range of lifestyle habits, including how often they brushed their teeth.

During a median follow-up of 10.5 years, 3% developed a-fib and 4.9%, developed heart failure. (Median means half were followed for less time, half for more.)

Those who brushed their teeth three or more times a day had a 10% lower risk of afib and a 12% lower risk of heart failure during the follow-up.

Chemical found in drinking water linked to tooth decay in children

West Virginia University

IMAGE: Being exposed to PFAS--a class of chemicals found in drinking water--has been linked to higher rates of cancer, heart disease, thyroid dysfunction and other conditions. WVU School of Dentistry researchers... view more 

Credit: Aira Burkhart/West Virginia University

Children with higher concentrations of a certain chemical in their blood are more likely to get cavities, according to a new study by West Virginia University School of Dentistry researchers.
Manufactured chemical g roups called perfluoroalkyl and polyfluoroalkyl substances are universal as a result of extensive manufacturing and use. Although manufacturers no longer use PFAS to make nonstick cookware, carpet, cardboard and other products, they persist in the environment. Scientists have linked them to a range of health problems--from heart disease to high cholesterol--but now R. Constance Wiener and Christopher Waters are exploring how they affect dental health.
They investigated whether higher concentrations of PFAS were associated with greater tooth decay in children. One of them--perfluorodecanoic acid--was linked to dental cavities. Their findings appear in the Journal of Public Health Dentistry.
"Due to the strong chemical bonds of PFAS, it is difficult for them to breakdown, which makes them more likely to be persistent within the environment, especially in drinking water systems," said Waters, who directs the School of Dentistry's research labs. "A majority of people may not be aware that they are using water and other products that contain PFAS."
The 629 children who participated in the study were 3 to 11 years old and were part of the National Health and Nutrition Examination Survey. Samples of the children's blood were analyzed for PFAS in 2013 and 2014. Their tooth decay and other factors--such as their race, their BMI and how often they brushed their teeth--were assessed.
Of the seven PFAS that Wiener and Waters analyzed, perfluorodecanoic acid was the one that correlated with higher levels of tooth decay.
"Perfluorodecanoic acid, in particular, has a long molecular structure and strong chemical bonds; therefore, it remains in the environment longer. As a result, it is more likely to have negative health consequences such as dental caries," said Dr. Wiener, an associate professor in the Department of Dental Practice and Rural Health.
But how does that influence happen? Wiener and Waters have a hypothesis. According to other research, perfluorodecanoic acid may disrupt the healthy development of enamel, which is what makes teeth hard. That disruption can leave teeth susceptible to decay.
However, when it comes to cavities, scientists haven't parsed perfluorodecanoic acid's mechanism of action yet. The topic warrants further investigation.
"While the findings of this study are important, there are some study limitations, and more work is needed to fully understand how this molecule impacts normal tooth formation," said Fotinos Panagakos, the School of Dentistry's vice dean for administration and research.
"The good news is that, in our study, about half of the children did not have any measurable amount of PFAS. Perhaps this is due to certain PFAS no longer being made in the US," Wiener said.
Another piece of good news is that the study reaffirmed the importance of dental hygiene and checkups. Children who brushed once a day or less frequently had significantly higher tooth decay than those who brushed at least twice daily.
Likewise, children who had not been to the dentist within the previous year were twice as likely to have higher rates of tooth decay than kids who hadn't.
So, even though parents cannot control what is in their children's drinking water, they can still protect their children's teeth by fostering thorough, regular brushing and scheduling dental exams.
The School of Dentistry will hold Give Kids a Smile Day on Friday, Feb. 7, at the Pediatric Dentistry Clinic. Dental students will treat more than 100 children for free that day. Each visit includes an exam, a cleaning, a fluoride treatment and--if appropriate--X-rays.

###

Citatio
Title: Perfluoroalkyls/polyfluoroalkyl substances and dental caries experience in children, ages 3-11 years, National Health and Nutrition Examination Survey, 2013-2014
DOI: 10.1111/jphd.12329
Link: https://pubmed.ncbi.nlm.nih.gov/31286520-perfluoroalkylspolyfluoroalkyl-substances-and-dental-caries-experience-in-children-ages-3-11-years-national-health-and-nutrition-examination-survey-2013-2014/

More than half of US opioid prescriptions for dental procedures exceeded 3-day supply recommendations

New largescale study in the American Journal of Preventive Medicine found overprescription of opioids by dentists common, particularly to patients at high risk for substance abuse, and that almost 1/3 of patients received more powerful drugs than needed

Elsevier

IMAGE: In this cross-sectional analysis of 542,958 dental visits by adult patients, between 1 in 4 and 1 in 2 opioid prescriptions exceeded the recommended morphine equivalents and days' supply for... view more 

Credit: Michelle S. Woods

Ann Arbor, February 4, 2020 - Dentists are among top prescribers of opioids in the US, however, whether their opioid prescribing exceeds guidance had not been investigated. A new study in the American Journal of Preventive Medicine, published by Elsevier, indicates that more than half of opioid prescriptions issued by dentists exceed the three-day supply recommended by the US Centers for Disease Control and Prevention (CDC) for acute dental pain management. The findings also show that 29 percent of dental patients received more powerful opioids than needed for expected post-procedure pain.
"Unlike national trends, opioid overprescribing by dentists is increasing. Our results should initiate a call to action to professional organizations and public health and advocacy groups to improve the guidelines for prescribing opioids for oral pain. As high prescribers of opioids writing prescriptions for a tenth of the opioids dispensed in the US, dentists should be included as part of the multi-faceted solution needed for the opioid epidemic," explained lead investigator Katie J. Suda, PharmD, MS, Professor, University of Pittsburgh School of Medicine, Division of General Internal Medicine, Pittsburgh, PA, USA.
The study used Truven Health MarketScan Research Databases to assess close to 550,000 dental visits by adult patients between 2011 and 2015, prior to the implementation of the 2016 CDC guidelines for pain management. These guidelines recommend first-line treatment using non-opioid analgesics for oral pain when possible. If stronger analgesics are needed after dental surgery, low-potency opioids (e.g., acetaminophen with codeine) are recommended instead of high-potency opioids (e.g., oxycodone). Moreover, three days or less of treatment is considered sufficient for typical oral pain. It is also a best practice for dentists to check their local prescription drug monitoring program (PDMP) before they write a prescription for any opioid to identify patients at risk of opioid abuse.
Investigators also found that the proportion of prescribed opioids that exceeded the recommended morphine equivalents increased in 2015. This was likely due to an increase in the quantity of hydrocodone tablets dispensed after the Food and Drug Administration's (FDA) rescheduling of hydrocodone from a schedule III to a schedule II drug in 2014. While hydrocodone rescheduling was associated with a decrease in hydrocodone prescribing nationally, this study's results suggest that this change resulted in an average increase of two tablets dispensed per hydrocodone prescription prescribed by dentists. Nationally, this increase translates to more than14 million additional hydrocodone tablets dispensed to patients after rescheduling hydrocodone to a schedule II drug.
"Similar to medical providers, dentists need to be provided resources to aid in their prescribing decisions for pain medications," commented Dr. Suda. "This should include clinical guidelines specific to oral pain and education on how to talk to their patients about treating their oral pain."
Co-investigator Susan A. Rowan, DDS, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA, emphasized that the demographic groups most impacted by overprescribing (patients aged 18 to 34 years, men, those living in the Southern US, and those receiving oxycodone) also carry a higher risk of addiction and overdose. She suggested that "additional studies are needed to evaluate the efficacy of the CDC 2016 prescribing guidelines subsequent to their introduction."
"Future studies and targeted efforts to reduce overprescribing would also be well motivated among older patients and others taking multiple other high risk medications such as benzodiazepines," added Gregory S. Calip, PharmD, MPH, PhD, College of, Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
Dr. Suda and co-investigators invite professional organizations and public health and advocacy groups to use the study's data to inform future efforts. In the interim, they recommend that individual dentists implement their own practice-specific guidelines, favoring ibuprofen plus acetaminophen and low-potency opioids for post-extraction pain management.
Using statistical modeling, investigators predict that overprescribing would decrease by more than 20 percent if oxycodone prescriptions were substituted with lower potency opioids (such as hydrocodone).