Can You Improve Periodontitis Treatments?

Written By Kevin Kerfoot / Reviewed By Ray Spotts

Periodontitis - or gum disease - is an inflammation of the gums and supporting structures of the teeth. It is one of the most common chronic diseases in the world, and in Germany, approximately 15 percent of people are affected by a particularly severe form of this disease. If left untreated, periodontitis will lead to tooth loss, and the disease also increases the risk of arthritis, cardiovascular disease and cancer.

In patients with periodontitis, a decrease in the diversity of the oral flora coincides with an increase in the frequency of E. gingivalis. So a team of researchers from Charité -- Universitätsmedizin Berlin was able to show that oral inflammation is associated with colonization by the oral parasite E. gingivalis. They found that a unicellular parasite commonly in the mouth plays a role in both severe tissue inflammation and tissue destruction. Most patients with severe and recurrent periodontitis - gum disease - showed an increased presence of the amoeba Entamoeba gingivalis inside their oral cavities. The effect of this amoeba is similar to that of Entamoeba histolytica, the parasite responsible for causing amebiasis. Once the parasite has invaded the gingival tissue, it feeds on its cells and causes tissue destruction.

The findings - published in the Journal of Dental Research - state that the two amoebae show similar mechanisms of tissue invasion and elicit a similar immune response in the host. "We have shown that an amoeba like E. gingivalis, which colonizes the oral cavity, will invade the oral mucosa and destroy gingival tissue,” says Professor Dr. Arne Schäfer, Head of the Periodontology Research Unit at Charité's Institute of Dental and Craniofacial Sciences. “This enables increased numbers of bacteria to invade the host tissue, which further exacerbates inflammation and tissue destruction.”

The team of researchers - the first to describe precise roles of E. gingivalis in the pathogenesis of inflammation - detected evidence of the amoeba in approximately 80 percent of patients with periodontitis, but in only 15 percent of healthy subjects. Their observations revealed that, after invading the gums, the parasites move within the tissue, feeding on and killing host cells. Cell culture experiments showed that infection with E. gingivalis slows the rate at which cells grow, eventually leading to cell death.

A clinical trial is underway to determine the extent to which the elimination of this amoeba might improve treatment outcomes in patients with periodontitis. The amoeba's role in inflammation shows distinct parallels to the pathogenesis of amebiasis. "E. gingivalis actively contributes to cell destruction inside the gingival tissue and stimulates the same host immune response mechanisms as E. histolytica during its invasion of the intestinal mucosa," Schäfer added. "This parasite, which is transmitted by simple droplet infection, is one potential cause of severe oral inflammation. We identified one infectious parasite whose elimination could improve treatment effectiveness and long-term outcomes in patients with gum disease. Current treatment concepts for periodontitis fail to consider the possibility of infection by this parasite or its successful elimination."

Understanding Periodontitis Bacteria

In a recent, large-scale study of microbial interactions, it was found to be untrue that bacteria living in the same space, like the mouth, have evolved collaborations so generous that they are not possible with outside bacteria. Research led by the Georgia Institute of Technology found that common mouth bacteria responsible for acute periodontitis fared better overall when paired with bacteria and other microbes that live anywhere but the mouth, including some commonly found in the colon or in dirt. Bacteria from the oral microbiome, by contrast, generally shared food and assistance more stingily with gum infector Aggregatibacter actinomycetemcomitans.

Aa often live in the mouth, and certain circumstances turn them into infectors. The researchers and their sponsors at the National Institutes of Health would like to know more about how Aa interacts with other microbes to gain insights that may eventually help fight acute periodontitis and other ailments. “Periodontitis is the most prevalent human infection on the planet after cavities,” says Marvin Whiteley, a professor in Georgia Tech’s School of Biological Sciences and the study’s principal investigator. “Those bugs get into your bloodstream every day, and there has been a long, noted correlation between poor oral hygiene and prevalence of heart disease.”

The findings are surprising because bacteria in a microbiome have evolved intricate interactions making it seem logical that those interactions would stand out as uniquely generous. Some mouth microbes even have special docking sites to bind to their partners, and much previous research has tightly focused on their cooperations. The recent study – published in Proceedings of the National Academy of Sciences - went broad. “We asked a bigger question: How do microbes interact with bugs they co-evolved with as opposed to how they would interact with microbes they had hardly ever seen. We thought they would not interact well with the other bugs, but it was the opposite,” Whiteley said.

Researchers manipulated and tracked nearly all of Aa’s roughly 2,100 genes using an emergent gene tagging technology while pairing Aa with 25 other microbes - about half from the mouth and half from other body areas or the environment. They did not examine the mouth microbiome as a whole because multi-microbial synergies would have made interactions incalculable. Instead, the researchers paired Aa with one other bug at a time - Aa plus mouth bacterium X, Aa plus colon bacterium Y, Aa plus dirt fungus Z, and so on. “We wanted to see specifically which genes Aa needed to survive in each partnership and which ones it could do without because it was getting help from the partner,” added Gina Lewis, a postdoctoral researcher in Whiteley’s lab and the study’s first author.

Understanding Mouth Microbiomes

The researchers looked at each of Aa’s genes necessary for survival while it infected a mouse - when Aa was the sole infector, when it partnered with a fellow mouth bacterium and when paired with a microbe from colon, dirt, or skin. “When Aa was by itself, it needed a certain set of genes to survive – like for breathing oxygen,” Lewin said. “It was striking that when Aa was with this or that microbe that it normally didn’t live around, it no longer needed a lot of its own genes. The other microbe was giving Aa things that it needed, so it didn’t have to make them itself.”

“Interactions between usual neighbors - other mouth bacteria - looked more frugal,” Whiteley added. “Aa needed a lot more of its own genes to survive around them, sometimes more than when it was by itself.” To understand “transposon sequencing,” picture a transposon as a DNA brick that cracks a gene, breaking its function. The brick also sticks to the gene and can be detected by DNA sequencing, thus tagging that malfunction. Every Aa bacterium in a pile of 10,000 had a brick in a random gene. If Aa’s partner bacterium, say, E. coli, picked up the slack for a broken function, Aa survived and multiplied even with the damaged gene, and researchers detected a higher number of bacteria containing the gene. Aa surviving with more broken genes meant a partner microbe was giving it more assistance. Aa bacteria with broken genes that a partner could not compensate for were more likely to die, reducing their count.

The mouth microbiome very likely does have unique relationships, but the study’s results point to not all relationships being cooperative. Some microbiomes could have high fences and share sparsely.  “One friend or enemy may be driving your behavior, and other microbes may just be standing around,” Lewin said. Smoking, poor hygiene, or diabetes - all associated with gum disease - might be damaging defensive microbiomes and allowing outside bacteria to help Aa attack gum tissue. It’s too early to know that, but Whiteley’s lab wants to dig deeper, and the research could have implications for other microbiomes.

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Written By:

With over 30 years of writing and editing experience for newspapers, magazines and corporate communications, Kevin Kerfoot writes about natural health, nutrition, skincare and oral hygiene for Trusted Health Products’ natural health blog and newsletters.

Reviewed By:

Founder Ray Spotts has a passion for all things natural and has made a life study of nature as it relates to health and well-being. Ray became a forerunner bringing products to market that are extraordinarily effective and free from potentially harmful chemicals and additives. For this reason Ray formed Trusted Health Products, a company you can trust for clean, effective, and healthy products. Ray is an organic gardener, likes fishing, hiking, and teaching and mentoring people to start new businesses. You can get his book for free, “How To Succeed In Business Based On God’s Word,” at www.rayspotts.com.

Photo by Ani Kolleshi on Unsplash