Oral bacteria at high levels could lead to Alzheimer’s disease

a tooth over a yellow background

by Celia Spell

Whether it be through a chomp, crunch or sip, food enters the body through the oral cavity, where a myriad of saliva bacteria starts breaking it down into sugars and proteins. With upwards of 700 different types of microorganisms in the mouth, recent research has shown that a balance of population levels is crucial to a healthy body but also a healthy mind.

Porphyromonas gingivalis, or P. gingivalis, is considered the primary pathogen in multiple forms of periodontal diseases, including adult periodontitis. It often resides at low levels in the mouths of healthy individuals, but at high levels it can spread from the mouth into the blood and is associated with systemic diseases like atherosclerosis, rheumatoid arthritis and diabetes and even with adverse pregnancy outcomes according to the National Institutes of Health. Recently researchers at MUSC have been looking at its role in Alzheimer’s disease.

Özlem Yilmaz, D.D.S., Ph.D., a professor at MUSC, has been researching P. gingivalis for years. A 2019 paper of hers published in the Journal of Oral Microbiology looked at this bacterium and its association with oral, gastrointestinal, and pancreatic cancers, and another from the Microbes and Infection journal in 2015 looked at its associations with systemic diseases in general. Both provide evidence for an association with P. gingivalis and diseases beyond oral cavity ones. She is currently working on a study evaluating its association with Alzheimer’s disease.

As the most common form of dementia, Alzheimer’s disease affects almost 6.7 million Americans over the age of 65 and is considered a neurodegenerative disease. And if P. gingivalis does indeed cause or contribute to the development of dementia, then it has to pass through the tightly regulated vessels of the central nervous system known as the blood-brain barrier.

As one of the leading labs in the world on this topic, Yilmaz and her team have been examining the intracellular life of this microorganism to understand whether it can pass that barrier and establish a silent infection in the brain. She says the question is particularly hard to decipher because the disease process for Alzheimer’s disease itself is still poorly understood.

“It’s complicated by the fact that people with disease already have compromised health, which could in turn compromise the blood-brain barrier,” she said. “We want to know if the microbe passes into the brain after their health declines or does it as part of the cause. That part is not clear to anyone yet.”

This past June, Yilmaz presented her data at the National Institutes of Aging Oral Health and Alzheimer’s and Related Dementias Workshop. Her multidisciplinary research team included MUSC researchers Onder Albayram, Ph.D., Eric Hamlett, Ph.D., Adviye Ergul, M.D., Ph.D., and Lori McMahon, Ph.D. They found intact forms of P. gingivalis in the brain bank tissue samples of people with Alzheimer’s disease as well as in their cerebrospinal fluid. When compared with tissue samples of those with other brain diseases that were not neurodegenerative, the team found no visible (or detectable) P. gingivalis that appeared to establish bacterial invasion in the analyzed brain tissues.

P. gingivalis bacteria under a microscope 
P. gingivalis (green) invasion into human brain microvascular endothelial cells (red, actin; blue, nuclei) visualized by high-resolution confocal microscopy. Scale bar, 20 µm. Credit: Yilmaz Lab, Bridgette Wellslager

P. gingivalis is also very stubborn – once it establishes a colony, it’s almost impossible to remove it with conventional antimicrobials. “My lab is focused on how it establishes such a successful intracellular life that makes the microorganism resistant to currently available antibacterial therapeutics,” Yilmaz said. “And what mechanisms can we identify to eliminate or decrease these high levels of bacteria that contribute to systemic disease later on.”

The blood-brain barrier was once thought to be sterile, with no bacteria crossing the threshold into the brain. Growing research is showing that’s not true, but more work is needed to determine what exactly can pass through and how.

Yilmaz says her team is still establishing the role P. gingivalis plays in neurodegenerative diseases like Alzheimer’s disease, but accepting that it passes the blood-brain barrier is a step in the right direction. After that, they’ll look into treatments and ways to decrease its levels in the mouth and throughout the body.

“The question is now,” she said, “if we can stop the infection in the mouth before it gets into the bloodstream and colonizes other areas of the body by knowing more about its mechanisms, and can we come up with a therapeutic intervention for people?”

Yilmaz also emphasizes the importance of proper dental care and says the best solution is to start with children when they’re young and continue with dental appointments every 6 months to a year consistently for the rest of their lives.

The mouth is an ecosystem and one that is particularly close to the brain. Even if proximity doesn’t play a factor, it does seem awfully close to travel from one to the other.