Bacteriophage Therapy: Tipping the Balance to Oral Health

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  1. Goal
  2. Background
  3. Gaps and Opportunities
  4. Specific Areas of Interest
  5. References

September 2023

Oral Opportunistic Pathogens & Viral Disease Program
Integrative Biology and Infectious Diseases Branch
Division of Extramural Research

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Goal

The goal of this concept is to encourage research to better understand bacteriophage biology in the oral cavity and to support eventual development of therapeutics. Despite the high abundance of bacteriophage in the oral cavity, they continue to be overlooked as mediators of health and disease. An increased understanding of the role of bacteriophage in the oral cavity could lead to the development and use of phage therapy.

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Background

The human oral cavity provides a portal of entry for viruses and bacteria. Metagenomics studies have identified a large population of viruses in the oral cavity, many of which were identified as bacteriophage--up to 108 phages exist in 1 ml of human saliva. Phages specific for bacteria in the oral cavity, including Lactobacillus, Actinomyces, Aggregatibacter, Fusobacterium, Enterococcus, Porphyromonas, and Streptococcus species have been identified. Despite the high abundance of bacteriophage in the oral cavity, their role as critical determinants of bacterial population structure/ecology and virulence remains unknown.

Phages have been shown to play various roles in the host, including influencing bacterial communities through predation, interacting with mammalian cells, and impacting the structure of biofilm communities. The ability of bacteriophage to penetrate biofilms has been shown to be more efficient than some antimicrobial treatments for biofilm removal, indicating that phages may serve as useful anti-bacterial agents in the oral cavity. Bacteriophage could even be engineered to release biofilm-degrading enzymes to further enhance biofilm breakdown. In addition to being highly efficient against biofilms, bacteriophage are strain specific and easy to isolate and manipulate, making them an ideal candidate to serve as a therapeutic. A benefit of phage therapy is that it does not boost antibiotic resistance. A 2021 report from CDC found that healthcare professionals prescribed over 211 million antibiotic prescriptions, 12% of which were prescribed by dentists. The overuse of antibiotic therapy has created resistant bacterial strains that have become a serious health threat. In response to antimicrobial resistance, researchers continue to explore bacteriophages as potential therapy. Although various Eastern European countries widely use phage-based treatments, there are no Food and Drug Administration (FDA)-approved phage therapies; use of phage therapy in the US has been under compassionate use conditions. The first U.S.-based clinical trials of phage therapy have only recently begun evaluating bacteriophage therapy in adults with cystic fibrosis who carry Pseudomonas aeruginosa in their lungs.

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Gaps and Opportunities

Although increasing knowledge suggests that bacteriophage play important roles in regulating microbial ecosystems, bacteriophage-bacteria interactions in the human oral cavity remains less understood. Addressing this gap in knowledge around the role of phages in the oral environment will not only allow for a better understanding of oral microbiome ecology but may also provide potential novel therapeutics for the prevention and treatment of oral disease. Phage therapy is used widely in other countries, and with the start of the first U.S. clinical trial underway, it is an excellent time to expand studies on oral phage biology to support eventual development of therapeutics.

While NIDCR supports a robust portfolio on oral microorganisms, including bacteria, fungi and viruses, there is a distinct gap in research related to phages. Across NIH, only about 60 awards have been made specifically focused on phage therapy; most were funded by NIAID. In 2021, NIAID supported 12 grants to address key knowledge gaps in the development of phages as preventative and therapeutic tools for bacterial infections, none of which include the oral cavity. The NIH common fund Human Virome Program (HVP) is under development and aims to characterize the many viruses that reside inside us without causing disease and to improve our understanding of how they impact human health. While phages are included in the HVP, the focus is not on infectious disease or therapeutics.

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Specific Areas of Interest

Much of the research pertaining to phage therapy in the oral cavity is still in the preliminary stages. While phages specific for numerous oral bacteria species have been identified and isolated, research is needed to increase our understanding of the roles and potential uses of bacteriophages in the oral cavity. Potential areas of research that could address current gaps beyond identifying and characterizing new bacteriophages from the oral cavity include, but are not limited to, the following:

  • Elucidating the roles of oral phages as drivers of bacterial diversity and dysbiosis in oral disease
  • Understanding the bacteriophage-bacteria relationship and effects on bacterial virulence, phage resistance, community structure, host physiology, and population dynamics
  • Defining direct and indirect antibacterial properties and antibiofilm activity of phages
  • Understanding phage-host interactions in vivo to establish basic tools to exploit phages as safe and effective modulators of oral microbial communities
  • Examining the therapeutic potential of bacteriophages to prevent or treat oral disease such as dental caries, gingivitis, and/or periodontal disease
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References

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Last Reviewed
December 2024