The Ohio State University College of Dentistry
 
     

The Breakthrough Relationship of Smoking to Gum Disease

Dr. Kumar

The detrimental effects of smoking are well known. Medical professionals and many people in the general public can recite the potential negative outcomes of tobacco use, from cancer to lung disease to gum disease. Now, the combination of advanced computational techniques and a novel scientific query has resulted in an understanding of how smoking causes severe periodontal disease.

Dr. Purnima Kumar and her research team in the Division of Periodontology at The Ohio State University College of Dentistry have discovered a compelling cause and effect relationship between smoking and periodontal disease. As a result, a significant change is emerging in clinical procedures for treating smokers. Recently, Dr. Kumar’s findings were published in Scientific American, Journal of Periodontology, Journal of Clinical Periodontology, PLOS ONE, and Infection and Immunity.

“It all begins with the biofilm, a normal, healthy collection of bacteria in the oral cavity,” said Dr. Kumar. Biofilms will form on moist surfaces in the body and elsewhere, including your kitchen counter, if conditions are favorable. In the oral cavity, the environment is very favorable, and biofilms form on the teeth and in the gingival sulcus or spaces between teeth and gums. “Good bacteria in biofilms can protect us by saturating the niche and preventing dangerous bacteria (pathogens) from colonizing. Biofilms also educate our immune system to recognize what are good and bad bacteria in the body,” she explained. However, biofilms can also become a runaway train, providing a breeding place for pathogenic bacteria that can quickly lead to periodontal disease and/or decay.

“We know that smoking increases your risk of getting severe periodontal disease and oral cancer,” Dr. Kumar explained. “Yet there is significant ambiguity in the literature about how this increased risk arises. Since bacteria outnumber human cells in our bodies by 10 to 1, and play such an important role in keeping us healthy, our research explores the ways that smoking can change the bacteria in the biofilm, from the moment they are acquired until the time the tooth is lost to disease.”

“Our research explores the ways that smoking can change the bacteria in the biofilm, from the moment they are acquired until the time the tooth is lost to disease.”
— Dr. Purnima Kumar

Dr. Kumar’s research clarified not only the unusual composition of a smoker’s biofilm, but also how the body recognizes and interacts with the novel bacteria. “We started this investigation in 2006 on smokers and nonsmokers with periodontal disease. What we found was a shocker,” she says. “Under their gingiva, smokers had many species that we did not know could be found in the oral cavity, and several species were systemic pathogens that usually cause diseases elsewhere in the body. As clinicians, we were treating everyone with exactly the same antibiotic…and should not have been.”

That was one issue. Then, a second issue emerged: Were the bacteria found in smokers a result of the periodontal disease or because these patients were smokers? In other words, does smoking raise the risk for developing periodontal disease?

“We found 20 smokers with healthy young mouths, who were coming into the clinics for regular cleaning. And found a similar, small group of nonsmokers. Both groups received a very thorough cleaning and we gave each participant a shield to use when brushing—to protect the bacteria in the gingiva from being flushed away. From plaque samples taken at one, two, seven, and 14 days after the cleaning, we sequenced the DNA in those scrapings and used flow cytometry to analyze 27 immune moderators. What we found was that within 24 hours, pathogens belonging to the genera Fusobacterium, Cardiobacterium, Synergistes, and Selenomonas, as well as respiratory pathogens belonging to the genera Hemophilus and Pseudomonas colonized the early biofilms of smokers. We thought we had done a good job cleaning their mouths, but they were not OK.”

Smokers also showed an early pro-inflammatory response to this colonization. Thus, smoking appears to affect both the biofilm composition and the host response to it. This stunning finding pointed to the impact of smoking and the impact of not correctly treating the pathogen risk.

As a follow-up, Dr. Kumar has now started a collaborative study where smokers have their teeth cleaned and then are given a probiotic that is specifically for the oral cavity. The study’s goal is to help the participants colonize some healthy bacteria in their biofilm. The study director, a visiting scholar from Egypt who is working on the clinical trial with the probiotics under Dr. Kumar’s supervision, will return to Ohio State in December to spend six months here, analyzing the data with Dr. Kumar. Another collaborator from Brazil is working with her to examine the effects of smoking on diabetic patients and their biofilms.

Dr. Kumar’s lab also consists of two PhD students, a post doc, two master’s students/residents, a major honors thesis program for four undergrads, a full-time research assistant, and a lot of computers. She describes the work environment as a “beautiful, fun place with a lot of Type A personalities who are eager to do their work.”

Microbiology today is much more than culturing organisms on agar plates and looking at them under a microscope, Dr. Kumar explained. “We investigate DNA and RNA sequences to identify the bacteria and find out what genes they express to survive and cause disease. Everything is done at the molecular level, not at the phenotypic level, and requires immense computing power to analyze these gigantic datasets of information. We use clusters of computers and operate in the cloud environment to speed things up. We are looking at bacterial genetics rather than host genetics (as would be the DNA analysis done to tailor cancer treatments to the individual), because the bacteria play an important role in disease and its prevention.”

With gene sequencing and powerful data analysis, researchers all over the world are discovering new bacteria in previously unsuspected locations or niches. “For example, we have seen a whole family of bacteria that were previously thought to be indigenous to a river or the ocean floor, and now inhabit the oral cavity. The whole world passes through the human mouth, some of the bacteria survive and thrive in this environment and others just pass through. It is possible that these and other groups of bacteria that originally were not associated with humans are now living in the human body. Powerful technologies have allowed us to tease out the changes in structure, function, and interactions that occur in a microbial community when such environmental stresses as smoking or acquired diseases like diabetes or obesity are factored in.”

In another study led by Dr. Kumar, a machine-learning algorithm was taught to identify a smoker and a nonsmoker based on their subgingival microbial profiles. When the algorithm was tested with bacterial sequences from 200 clinically healthy smokers and nonsmokers, it was able to pick out a smoker 100 percent of the time, indicating that even when we think our patients are clinically healthy, they may not be.

Among more than a dozen other research projects in Dr. Kumar’s lab, one study is looking at smokers vs. nonsmokers with diabetes to type out the bacteria. In another study, subjects are being paid to cease smoking and stay that way to allow researchers to follow the transformational changes in their bacteria. Parameters include a comparison of smoking cessation to weight loss. Said Dr. Kumar, “If you are a normal-weight person and quit smoking, what happens? If you are obese and you quit smoking, what happens? If you were obese and lost weight and quit, what happens?”

The results of Dr. Kumar’s data play out like this: If you are a smoker, you have a 16-fold increase in risk for a pathogenic community compared to a nonsmoker; if you are diabetic, add another 10-fold increase (now 26-fold); and if you are also obese, add another four-fold (20-fold risk compared to a nonsmoker).

So how does all this research move out into clinical practice? “What we do has direct clinical correlation. Every day I say to my patients, here is my data and it applies to you. A lot of what is happening to you is from you. Quit smoking and it can benefit you,” she said. “And one of the first things we did as a result of study was to use a different antibiotic for smokers with periodontal disease, because it works better for them. We now know how to profile these patients and we have a much better idea of how to treat them.”

“We have to be very aggressive in treating patients who smoke; see them more often, clean very carefully, and watch their periodontal tissue because they are high-risk individuals for periodontal disease. That’s the message we carry to clinicians—these are our most vulnerable patients.”