Potential Breakthroughs in Treating Oral Disease Through Better Understanding of the Oral Microbiome

Most people think of bacteria as the enemy, but scientists at the J. Craig Venter Institute (JCVI) are exploring ways to harness bacteria and phages (the viruses that infect bacteria) as a new way to fight infection. JCVI scientist, Anna Edlund, PhD, is leading one of our efforts to understand the human oral microbiome and learn what role bacteria play in both oral health and disease.

Potential Breakthroughs in Treating Oral Disease Through Better Understanding of the Oral Microbiome

Most people think of bacteria as the enemy, but scientists at the J. Craig Venter Institute (JCVI) are exploring ways to harness bacteria and phages (the viruses that infect bacteria) as a new way to fight infection. JCVI scientist, Anna Edlund, PhD, is leading one of our efforts to understand the human oral microbiome and learn what role bacteria play in both oral health and disease.

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Inflammatory gum disease (gingivitis/periodontal disease) and tooth decay are not only the two biggest threats to oral health, but they also contribute to systemic diseases such as diabetes and cardiovascular disease. Oral health concerns begin early, with cavities being one of the most chronic conditions in the United States in children and adolescents.

Dr. Edlund wants to determine the function of the hundreds of microbes living in the mouth, especially their relation to diseases, and identify non-invasive treatments and therapies specific to oral disease.

The Phage Cocktail Approach

Bacteriophages are viruses that infect and thrive inside bacteria. They are one of the most abundant biological entities on earth and are found everywhere there are bacteria. Because of their ability to attack bacteria, phages have been used as antibiotics for nearly a century in the former Soviet Union, Central Europe, and France. Given the troubling rise of antibiotic resistance, phage therapy could be a new weapon in the war against infection.

The phage therapy approach focuses on developing a potential treatment to kill specific oral bacterial pathogens, removing harmful biofilms, and re-colonizing the mouth with healthy bacteria to prevent re-growth.

To do this, we will first isolate and purify a diverse community of phage. Specific phage activity will be cataloged, and then tested individually against known disease-causing oral bacteria. Cocktails of effective phages will be tested against a broader group of bacteria. A future goal of the project is to then test the phage cocktails in mouse models to confirm viable candidates to move into clinical testing in humans.

The Healthy Bacteria Approach

While probiotics are widely used globally, currently none of the available probiotics on the market have been scientifically proven to prevent or treat oral disease. A goal of the “healthy bacteria approach” is to explore and enhance understanding of interactions between probiotic bacteria in oral biofilms, as well as between bacteria and human host cells.

Recently, Dr. Edlund’s laboratory discovered about 5,600 novel gene clusters from the human oral microbiome that are genetically similar to known natural products. Natural products play important roles in mediating communication between human and bacterial cells, suggesting that the human mouth is a highly diverse and underexplored environment for the discovery of novel therapeutics. In this project, the team will apply their new knowledge to formulate probiotics that target specific pathogens, such as those that cause tooth decay and thrush.

We believe that this research will result in an arsenal of oral bacteria that produce novel natural products which play a major role in promoting oral health. This, in turn, will lead to future studies, including activity screening in animal models, and clinical testing of probiotics in humans.

Publications

Precision Reengineering of the Oral Microbiome for Caries Management.
Advances in dental research. 2019-11-01; 30.2: 34-39.
PMID: 31633390
Klebsiella and Providencia emerge as lone survivors following long-term starvation of oral microbiota.
Proceedings of the National Academy of Sciences of the United States of America. 2019-04-23; 116.17: 8499-8504.
PMID: 30975748
Identification of the Bacterial Biosynthetic Gene Clusters of the Oral Microbiome Illuminates the Unexplored Social Language of Bacteria during Health and Disease.
mBio. 2019-04-16; 10.2:
PMID: 30992349
Exploiting the Oral Microbiome to Prevent Tooth Decay: Has Evolution Already Provided the Best Tools?
Frontiers in microbiology. 2019-01-11; 9.3323.
PMID: 30687294
Characterization of the Trehalose Utilization Operon in Streptococcus mutans Reveals that the TreR Transcriptional Regulator Is Involved in Stress Response Pathways and Toxin Production.
Journal of bacteriology. 2018-06-15; 200.12:
PMID: 29632089

Funding

This project is currently seeking a funding partner. Please contact the JCVI Development Office at development@jcvi.org to learn more.