E-cigarette (e-cig) use is rising, but much is unknown about the effects of its vapor. This vapor contains chemicals such as propylene glycol, a known antimicrobial, and nicotine, whose derivatives are carcinogenic. Here, we study the effects of vaping on resident bacteria of the oral cavity and on oral cell inflammation. Oral streptococci are major residents in the oral cavity, with S. mutans the primary cause of dental caries. Growth and biofilm formation have been shown to be enhanced upon exposure to traditional cigarette smoke in vitro. In this study, we analyzed the effects of e-cig vapor on growth and biofilm formation in S. mutans, S. sanguinis, and S. gordonii. Organisms and oral epithelial cells were treated using nicotine-free and 3mg nicotine vapor, as well as double-shot menthol freeze flavored 3mg nicotine vapor in a vape chamber designed to phenocopy physiologically relevant exposure. Nicotine-independent inhibition of growth occurred upon exposure in all three bacterial species. Interestingly, biofilm formation was enhanced in the S. mutans while decreased in S. sanguinis and S. gordonii. Epithelial cells showed activation of survival pathways by Western Blot upon exposure to only e-cigarette vapor as well as co-culturing of bacterial and oral epithelial cells at a multiplicity of infection of one The pioneer colonizers S. gordonii and S. sanguinis generally antagonize caries-causing S. mutans, which can become a predominant member of the community under appropriate conditions, leading to dental caries formation. The observed decrease in the biofilm formation of the commensals S. sanguinis and S. gordonii upon e-cig vapor exposure indicates the opportunistic colonization of S. mutans, whose biofilm-forming abilities increased. Following e-cig usage, dental caries and cancer in the oral epithelium may result from this dysbiosis of the microbiome.