Periodontitis is a common form of serious gum disease that can slowly damage the tissues and bone that hold teeth in place.
Researchers at Nagoya University in Japan have now developed a new treatment designed to kill one of the key bacteria linked to the disease while leaving many helpful mouth bacteria unharmed.
The research was published in the Journal of Translational Medicine. The experimental treatment uses antibodies and near-infrared light to find and destroy Porphyromonas gingivalis, often shortened to P. gingivalis, a bacterium that can play an important role in the development and worsening of periodontitis.
The human mouth naturally contains a large community of bacteria. Many of these microbes are harmless or helpful, and a healthy mouth depends partly on keeping this community in balance.
Problems can begin when harmful bacteria become too influential. P. gingivalis is considered especially important because even when it is not the most common bacterium in the mouth, it can interfere with the immune system and help create conditions that favor inflammation and disease.
Over time, ongoing inflammation around the teeth can damage the gums and the bone underneath them. If periodontitis becomes severe and is not controlled, teeth may loosen and eventually be lost.
Dentists usually treat periodontitis by removing plaque and hardened deposits from around and below the gumline. In some situations, antibiotics or other bacteria-killing approaches may also be used, particularly when the disease is difficult to control.
However, treatments that kill bacteria broadly can create another problem. They may remove helpful bacteria along with the harmful ones, disturbing the natural microbial community that normally lives in the mouth.
Kazuhide Sato of Nagoya University explained that existing approaches, including antibiotics and antimicrobial photodynamic therapy, can affect both harmful and beneficial bacteria. Some methods may also cause bacteria to break apart and release substances such as lipopolysaccharide, or LPS, which can stimulate inflammation.
The Nagoya University team therefore looked for a more selective way to attack the bacteria involved in disease. Their idea was adapted from near-infrared photoimmunotherapy, a technology originally developed to target cancer cells.
The basic idea is similar to giving the treatment a biological address label. An antibody recognizes a specific target, while a light-sensitive dye attached to that antibody can be activated with near-infrared light after it has reached the target.
For the new gum disease treatment, the researchers used IgY antibodies obtained from egg yolks. Hens were immunized against P. gingivalis so that their eggs contained antibodies able to recognize the bacterium.
The team attached these antibodies to a light-sensitive dye. Because IgY antibodies can be produced in relatively large amounts and at comparatively low cost, the researchers believe they could be useful if the treatment eventually moves toward clinical use.
The scientists named their approach near-infrared photo-antibacterial targeting therapy, or NIR-PAT². They tested it in laboratory-grown cells and bacteria and then studied its effects in mice with periodontitis.
In the laboratory experiments, the antibody-dye combination attached mainly to P. gingivalis rather than other bacteria or healthy human gum cells. When near-infrared light was applied, the treatment damaged the outer membrane of the targeted bacteria and killed them.
Microscope images showed an interesting difference between the new method and conventional antimicrobial photodynamic therapy. NIR-PAT² created small holes in the bacterial membrane while much of the bacterial structure remained intact, whereas the conventional light treatment caused much more complete destruction.
That difference could matter because violently breaking bacteria apart may release inflammatory material from inside or around the bacterial cell. A treatment that kills the target without causing the same degree of breakdown might potentially reduce this unwanted effect, although its importance in patients still needs to be tested.
The researchers also examined whether the treatment damaged healthy human gum cells. Their tests found no significant injury from the targeted treatment, while conventional antimicrobial photodynamic therapy caused cell damage and slowed healing under the experimental conditions.
The mouse experiments provided another encouraging result. Animals treated with the new method had significantly less loss of the bone that supports the teeth, suggesting that selectively removing P. gingivalis could reduce some of the damage caused by periodontitis.
Saliva samples also showed that the treatment changed the bacterial community in a more selective way. P. gingivalis was reduced while beneficial Streptococcus bacteria were preserved, unlike antibiotics and conventional light therapy, which removed a broader range of microbes.
This selectivity is one of the most important parts of the study. Modern research increasingly shows that health is not simply about removing as many bacteria as possible, but about maintaining a stable community in which harmful species do not take control.
Still, the researchers stress that periodontitis is more complicated than a single bacterium. Many different microbes can contribute to the disease, and their effects can change depending on how they interact with one another and with a person’s immune system.
The team plans to use artificial intelligence to examine large sets of publicly available information about oral bacteria. The goal is to identify other important bacterial targets and understand which combinations of microbes may be most important in different forms of gum disease.
Such work could eventually lead to treatments that are tailored more closely to an individual patient’s oral bacterial community. Instead of using a broad treatment that kills many microbes, doctors or dentists might one day target only the bacteria that are driving disease in that person.
The research may also be relevant beyond the mouth. Periodontitis has been associated with conditions including diabetes and rheumatoid arthritis, although an association does not mean gum disease directly causes those illnesses.
Overall, the study offers a promising proof of concept for a more precise way to treat periodontitis. The strongest finding is that the therapy was able to target P. gingivalis while largely preserving other bacteria and healthy cells, and it also reduced bone loss in a mouse model.
However, the results should not yet be taken as evidence that the treatment is ready for routine dental care. Much of the work was performed in laboratory systems and mice, and human mouths are more complex, with many bacterial species, differences in immune responses, dental plaque, saliva and varying stages of gum disease.
Future studies will need to establish whether the therapy is safe and effective in people, how often treatment would be needed, how light could be delivered to difficult areas around teeth, and whether targeting several harmful species is necessary.
If those challenges can be solved, NIR-PAT² could represent a shift from broad bacteria-killing treatments toward much more selective control of the microbes that drive gum disease.
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Source: Nagoya University.
