Combining Bacteriophage-Mediated Decolonization with Microbial Engraftment to Foster Sustained Supragingival Microbiome Modulation for Enhanced Anti-Cariogenic Therapy

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Vulcan Biologics plans to harness the power of synthetic biology to enable persistent and stable modulation of the oral microbiome for the prevention of dental caries. Caries are characterized by the acidification and degradation of tooth enamel when dietary sugars come into contact with dental biofilms (plaque). Affecting an estimated 42% of children, 59% of adolescents, and 92% of adults in the U.S., dental caries is the most prevalent chronic disease in humans. Caries can be accompanied by serious comorbidities and complications, including pain, abscesses, dental sepsis, and even death. Caries contribute to diminished quality of life and account for an estimated $5.4 billion in lost productivity each year. Despite U.S. spending in excess of $124 billion each year, current methods to prevent caries, including brushing/flossing and fluoride applications, have done little to reduce the overall prevalence of caries in the population in the last decade. Thus, more effective measures to prevent dental caries remain a critical unmet need. The last two decades have brought an increasing awareness of the role of the oral microbiome in dental caries pathogenesis, revealing that caries development and progression are accompanied by changes in the proportions of particular bacterial species. Streptococcus mutans is a naturally occurring member of the oral microbiota and the principal etiological agent of dental decay in humans. While a few small molecules capable of selectively killing S. mutans have been identified, their effects are likely to be short-lived. As an alternative, Vulcan Biologics proposes a tripartite approach for the persistent and stable reprogramming of the oral microbiome to reduce or eliminate the prevalence of S. mutans. This approach is based on combining the application of bacteriophages— —with viruses that exclusively target bacteria but do not affect eukaryotic cells selected bacteria that should provide a probiotic effect and nutrients (prebiotics) that are specific to the protective probiotic bacteria. In detail, this three-pronged, combined-arms approach involves: i) the use of virulent bacteriophages to target the specific niche within the oral microbiome that should be decolonized for the target, in this case S. mutans, ii) administration of an engineered or evolved replacement protective probiotic, e.g. Lactobacillus spp., to be engrafted into the oral niche, and iii) provisioning of a prebiotic or combination of prebiotics that uniquely benefit the colonizing strains to promote adherence and long-term engraftment. This decolonization/recolonization (Decon-Recon) strategy has the potential to succeed where previous attempts to modulate the microbiome have failed: overcoming the resistance of established microbial communities to the permanent engraftment of newcomers.