Dentists aren’t known to tell people not to brush, but that’s what happened on the way to a breakthrough.
After asking study participants not to brush half their teeth for three weeks, researchers discovered that genetic differences make some people more susceptible to chronic inflammatory diseases that cause a host of health loss and disability.
Scientists have scrambled to determine why some individuals are more vulnerable to inflammation even with good hygiene habits and healthy lifestyles. Understanding that variation could have a major impact in the prevention of periodontitis, or severe gum disease, through care personalized to each individual’s risk for inflammation.
And periodontal disease has implications far beyond the mouth, for other chronic conditions such as atherosclerosis, asthma, rheumatoid arthritis, inflammatory bowel disease and others.
“Chronic inflammation leads to devastating disorders throughout the body that are interrelated – the presence of one inflammatory disease often increases the risk for others,” said Georgios A. Kotsakis, DDS, MS, associate professor of periodontics and director of the ITI Implantology Scholarship Center at The University of Texas Health Science Center at San Antonio, also known as UT Health San Antonio.
Dr. Kotsakis, along with University of Washington researchers and others, is co-author of the study published in the Proceedings of the National Academy of Sciences: “Human variation in gingival inflammation,” which pointed up a previously unrecognized range of human inflammatory response.
A different approach
The study participants who partially abstained from brushing were tracked with weekly dental examinations.
Most scientific studies of how bacteria cause inflammation are performed in mice. But with this study using “reversible experimental gingivitis” in humans, dental hygiene was withheld from select teeth to allow bacteria to accumulate naturally, without long-term effects.
Experimental gingivitis has been done before, but in “cross-sectional” studies that observed inflamed gums at a single point, usually at the end. The new study marked the first “longitudinal” analysis that looked at inflammation, bacterial composition and the participants’ immune response at seven different times from start to end.
In the new study, researchers sampled both bacteria and immune cells around the teeth, collecting secreted blood material containing “neutrophils,” which the body employs to fight microbes. They found a previously unidentified range of genetic variation that drove the body’s response to bacteria, with “low-responders” showing minimal activation of immune mechanisms.
Conversely, “high-responders” showed more intense gingivitis, an important marker of tissue-destructive disease, overreacting to the microbes. The neutrophils in these high-inflammatory types released a number of protein molecules called chemokines, which can signal deeper tissue inflammation and even bone destruction in the body.
While low- and high-responding types have been suggested in previous cross-sectional observations, investigators this time identified a third type, which they called “slow-responders,” between the low and high levels. These individuals demonstrated delayed inflammation to bacterial buildup, which revealed a novel protective mechanism that humans have that may spare tissue and bone during inflammation.
“This finding paves the way for using the molecular pathways identified in this study to screen individuals at high risk for disease and initiating tailored, preventive regimens across an array of chronic diseases,” said Dr. Kotsakis, who is a diplomate of the American Board of Periodontology.
His Translational Periodontal Research Lab at UT Health San Antonio co-led the advanced statistical analysis of the study. The study’s methods allowed the researchers to track the changes over time and see differences not detected in previous cross-sectional studies.
Good and bad bacteria
Further, researchers used DNA sequencing to identify all bacteria around the teeth, focusing on how “bad” bacteria causing inflammation might accumulate faster or slower in each person, as opposed to “good” bacteria that can fight infection. Dr. Kotsakis said the researchers found striking differences.
“In the high responders to inflammation, there was much faster colonization of the tissue with pathogenic bad bacteria, and very early reductions in the good bacteria that protect against inflammation,” he said.
As probiotics with their good bacteria have been shown to aid digestive health, he said, the study’s findings could lead to candidate probiotics developed as a new preventive strategy against inflammatory disease.
Human variation in gingival inflammation
Shatha Bamashmous, Georgios A. Kotsakis, Kristopher A. Kerns, Brian G. Leroux, Camille Zenobia, Dandan Chen, Harsh M. Trivedi, Jeffrey S. McLean and Richard P. Darveau
First published: July 6, 2021, Proceedings of the National Academy of Sciences